The Experts below are selected from a list of 3384 Experts worldwide ranked by ideXlab platform

Brian C Lewis - One of the best experts on this subject based on the ideXlab platform.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a75 overexpression of wnt1 induces ovarian type stroma that resemble human pancreatic Mucinous Cystic Neoplasm mcn
    Cancer Research, 2012
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, Victoria Appleman, Brian Quattrochi, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic Mucinous Cystic Neoplasm (MCN), a Cystic tumor of the pancreas with a predominant female gender bias, occurs primarily in the body and tail of the pancreas and is characterized by the presence of a Mucinous epithelium and ovarian-type stroma. To determine the involvement of Wnt ligand-induced signaling in pancreatic tumorigenesis, we combined the established LSL-KrasG12D, Ptf1a-cre model with the elastase-tva transgenic mouse to facilitate the delivery of avian leukosis virus-based RCASWnt1 viruses to the pancreatic epithelium. We found that female mice injected with RCAS-Wnt1, but not RCAS-GFP, commonly developed unilocular or multilocular cysts, sometimes including hemorrhagic contents (so called chocolate cyst), in the pancreas body and tail. The Cystic lesions were composed of the characteristic ovarian-type stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR) expression; however, they lacked the typical Mucinous epithelium. Interestingly, activation of Wnt/β-catenin and PCP signaling pathways – as determined by nuclear β-catenin, p-JNK and p-Rock2 positivity – was detected in the stroma, but not the cyst epithelium. Analysis of human MCN cases identified activation of both the Wnt/β-catenin and PCP signaling pathways in the ovarian-type stroma, but not the cyst epithelium, consistent with our findings in the mouse model. Together, these data suggest that activation of the canonical and non-canonical Wnt signaling pathways stimulates the development of the ovarian-type stroma observed in pancreatic MCN and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David Driscoll, David S. Klimstra, Wilfredo DeJesus-Monge, Victoria Appleman, Brian Quattrochi, Brian C. Lewis. Overexpression of Wnt1 induces ovarian-type stroma that resemble human pancreatic Mucinous Cystic Neoplasm (MCN). [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A75.

Makoto Sano - One of the best experts on this subject based on the ideXlab platform.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a75 overexpression of wnt1 induces ovarian type stroma that resemble human pancreatic Mucinous Cystic Neoplasm mcn
    Cancer Research, 2012
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, Victoria Appleman, Brian Quattrochi, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic Mucinous Cystic Neoplasm (MCN), a Cystic tumor of the pancreas with a predominant female gender bias, occurs primarily in the body and tail of the pancreas and is characterized by the presence of a Mucinous epithelium and ovarian-type stroma. To determine the involvement of Wnt ligand-induced signaling in pancreatic tumorigenesis, we combined the established LSL-KrasG12D, Ptf1a-cre model with the elastase-tva transgenic mouse to facilitate the delivery of avian leukosis virus-based RCASWnt1 viruses to the pancreatic epithelium. We found that female mice injected with RCAS-Wnt1, but not RCAS-GFP, commonly developed unilocular or multilocular cysts, sometimes including hemorrhagic contents (so called chocolate cyst), in the pancreas body and tail. The Cystic lesions were composed of the characteristic ovarian-type stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR) expression; however, they lacked the typical Mucinous epithelium. Interestingly, activation of Wnt/β-catenin and PCP signaling pathways – as determined by nuclear β-catenin, p-JNK and p-Rock2 positivity – was detected in the stroma, but not the cyst epithelium. Analysis of human MCN cases identified activation of both the Wnt/β-catenin and PCP signaling pathways in the ovarian-type stroma, but not the cyst epithelium, consistent with our findings in the mouse model. Together, these data suggest that activation of the canonical and non-canonical Wnt signaling pathways stimulates the development of the ovarian-type stroma observed in pancreatic MCN and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David Driscoll, David S. Klimstra, Wilfredo DeJesus-Monge, Victoria Appleman, Brian Quattrochi, Brian C. Lewis. Overexpression of Wnt1 induces ovarian-type stroma that resemble human pancreatic Mucinous Cystic Neoplasm (MCN). [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A75.

David S. Klimstra - One of the best experts on this subject based on the ideXlab platform.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a75 overexpression of wnt1 induces ovarian type stroma that resemble human pancreatic Mucinous Cystic Neoplasm mcn
    Cancer Research, 2012
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, Victoria Appleman, Brian Quattrochi, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic Mucinous Cystic Neoplasm (MCN), a Cystic tumor of the pancreas with a predominant female gender bias, occurs primarily in the body and tail of the pancreas and is characterized by the presence of a Mucinous epithelium and ovarian-type stroma. To determine the involvement of Wnt ligand-induced signaling in pancreatic tumorigenesis, we combined the established LSL-KrasG12D, Ptf1a-cre model with the elastase-tva transgenic mouse to facilitate the delivery of avian leukosis virus-based RCASWnt1 viruses to the pancreatic epithelium. We found that female mice injected with RCAS-Wnt1, but not RCAS-GFP, commonly developed unilocular or multilocular cysts, sometimes including hemorrhagic contents (so called chocolate cyst), in the pancreas body and tail. The Cystic lesions were composed of the characteristic ovarian-type stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR) expression; however, they lacked the typical Mucinous epithelium. Interestingly, activation of Wnt/β-catenin and PCP signaling pathways – as determined by nuclear β-catenin, p-JNK and p-Rock2 positivity – was detected in the stroma, but not the cyst epithelium. Analysis of human MCN cases identified activation of both the Wnt/β-catenin and PCP signaling pathways in the ovarian-type stroma, but not the cyst epithelium, consistent with our findings in the mouse model. Together, these data suggest that activation of the canonical and non-canonical Wnt signaling pathways stimulates the development of the ovarian-type stroma observed in pancreatic MCN and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David Driscoll, David S. Klimstra, Wilfredo DeJesus-Monge, Victoria Appleman, Brian Quattrochi, Brian C. Lewis. Overexpression of Wnt1 induces ovarian-type stroma that resemble human pancreatic Mucinous Cystic Neoplasm (MCN). [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A75.

David R Driscoll - One of the best experts on this subject based on the ideXlab platform.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a75 overexpression of wnt1 induces ovarian type stroma that resemble human pancreatic Mucinous Cystic Neoplasm mcn
    Cancer Research, 2012
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, Victoria Appleman, Brian Quattrochi, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic Mucinous Cystic Neoplasm (MCN), a Cystic tumor of the pancreas with a predominant female gender bias, occurs primarily in the body and tail of the pancreas and is characterized by the presence of a Mucinous epithelium and ovarian-type stroma. To determine the involvement of Wnt ligand-induced signaling in pancreatic tumorigenesis, we combined the established LSL-KrasG12D, Ptf1a-cre model with the elastase-tva transgenic mouse to facilitate the delivery of avian leukosis virus-based RCASWnt1 viruses to the pancreatic epithelium. We found that female mice injected with RCAS-Wnt1, but not RCAS-GFP, commonly developed unilocular or multilocular cysts, sometimes including hemorrhagic contents (so called chocolate cyst), in the pancreas body and tail. The Cystic lesions were composed of the characteristic ovarian-type stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR) expression; however, they lacked the typical Mucinous epithelium. Interestingly, activation of Wnt/β-catenin and PCP signaling pathways – as determined by nuclear β-catenin, p-JNK and p-Rock2 positivity – was detected in the stroma, but not the cyst epithelium. Analysis of human MCN cases identified activation of both the Wnt/β-catenin and PCP signaling pathways in the ovarian-type stroma, but not the cyst epithelium, consistent with our findings in the mouse model. Together, these data suggest that activation of the canonical and non-canonical Wnt signaling pathways stimulates the development of the ovarian-type stroma observed in pancreatic MCN and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David Driscoll, David S. Klimstra, Wilfredo DeJesus-Monge, Victoria Appleman, Brian Quattrochi, Brian C. Lewis. Overexpression of Wnt1 induces ovarian-type stroma that resemble human pancreatic Mucinous Cystic Neoplasm (MCN). [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A75.

Wilfredo E Dejesusmonge - One of the best experts on this subject based on the ideXlab platform.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm
    Cancer Research, 2015
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed Mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical Mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces Mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.

  • abstract a75 overexpression of wnt1 induces ovarian type stroma that resemble human pancreatic Mucinous Cystic Neoplasm mcn
    Cancer Research, 2012
    Co-Authors: Makoto Sano, David R Driscoll, Wilfredo E Dejesusmonge, Victoria Appleman, Brian Quattrochi, David S. Klimstra, Brian C Lewis
    Abstract:

    Pancreatic Mucinous Cystic Neoplasm (MCN), a Cystic tumor of the pancreas with a predominant female gender bias, occurs primarily in the body and tail of the pancreas and is characterized by the presence of a Mucinous epithelium and ovarian-type stroma. To determine the involvement of Wnt ligand-induced signaling in pancreatic tumorigenesis, we combined the established LSL-KrasG12D, Ptf1a-cre model with the elastase-tva transgenic mouse to facilitate the delivery of avian leukosis virus-based RCASWnt1 viruses to the pancreatic epithelium. We found that female mice injected with RCAS-Wnt1, but not RCAS-GFP, commonly developed unilocular or multilocular cysts, sometimes including hemorrhagic contents (so called chocolate cyst), in the pancreas body and tail. The Cystic lesions were composed of the characteristic ovarian-type stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR) expression; however, they lacked the typical Mucinous epithelium. Interestingly, activation of Wnt/β-catenin and PCP signaling pathways – as determined by nuclear β-catenin, p-JNK and p-Rock2 positivity – was detected in the stroma, but not the cyst epithelium. Analysis of human MCN cases identified activation of both the Wnt/β-catenin and PCP signaling pathways in the ovarian-type stroma, but not the cyst epithelium, consistent with our findings in the mouse model. Together, these data suggest that activation of the canonical and non-canonical Wnt signaling pathways stimulates the development of the ovarian-type stroma observed in pancreatic MCN and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David Driscoll, David S. Klimstra, Wilfredo DeJesus-Monge, Victoria Appleman, Brian Quattrochi, Brian C. Lewis. Overexpression of Wnt1 induces ovarian-type stroma that resemble human pancreatic Mucinous Cystic Neoplasm (MCN). [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A75.