The Experts below are selected from a list of 678 Experts worldwide ranked by ideXlab platform
Traci R. Lyons - One of the best experts on this subject based on the ideXlab platform.
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Deciphering Pro-Lymphangiogenic Programs during Mammary Involution and Postpartum Breast Cancer.
Frontiers in oncology, 2016Co-Authors: Virginia F. Borges, Alan M. Elder, Traci R. LyonsAbstract:Postpartum breast cancers are a highly metastatic subset of young women’s breast cancers defined as breast cancers diagnosed in the postpartum period or within 5 years of last child-birth. Women diagnosed with postpartum breast cancer are nearly twice as likely to develop metastasis and to die from breast cancer when compared to nulliparous women. Additionally, epidemiological studies utilizing multiple cohorts also suggest that nearly half of all breast cancers in women aged
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deciphering pro lymphangiogenic programs during Mammary Involution and postpartum breast cancer
Frontiers in Oncology, 2016Co-Authors: Virginia F. Borges, Alan M. Elder, Traci R. LyonsAbstract:Postpartum breast cancers are a highly metastatic subset of young women’s breast cancers defined as breast cancers diagnosed in the postpartum period or within 5 years of last child-birth. Women diagnosed with postpartum breast cancer are nearly twice as likely to develop metastasis and to die from breast cancer when compared to nulliparous women. Additionally, epidemiological studies utilizing multiple cohorts also suggest that nearly half of all breast cancers in women aged <45 qualify as postpartum cases. Understanding the biology that underlies this increased risk for metastasis and death may lead to identification of targeted interventions that will benefit the large number of young women with breast cancer who fall into this subset. Preclinical mouse models of postpartum breast cancer have revealed that breast tumor cells become more aggressive if they are present during the normal physiologic process of postpartum Mammary gland Involution in mice. As Involution appears to be a period of lymphatic growth and remodeling, and human postpartum breast cancers have high peri-tumor lymphatic vessel density (LVD) and increased incidence of lymph node metastasis37,41, we propose that novel insight into is to be gained through the study of the biological mechanisms driving normal postpartum Mammary lymphangiogenesis as well as in the microenvironment of postpartum tumors.
Harold L. Moses - One of the best experts on this subject based on the ideXlab platform.
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tgf β promotes cell death and suppresses lactation during the second stage of Mammary Involution
Journal of Cellular Physiology, 2009Co-Authors: Brian Bierie, Agnieszka E. Gorska, Daniel G. Stover, Harold L. MosesAbstract:Transforming growth factor beta (TGF-beta) ligands are known to regulate virgin Mammary development and contribute to initiation of post-lactation Involution. However, the role for TGF-beta during the second phase of Mammary Involution has not been addressed. Previously, we have used an MMTV-Cre transgene to delete exon 2 from the Tgfbr2 gene in Mammary epithelium, however we observed a gradual loss of T beta RII deficient epithelial cells that precluded an accurate study of the role for TGF-beta signaling during Involution timepoints. Therefore, in order to determine the role for TGF-beta during the second phase of Mammary Involution we have now targeted T beta RII ablation within Mammary epithelium using the WAP-Cre transgene [T beta RII(WKO)Rosa26R]. Our results demonstrated that TGF-beta regulates commitment to cell death during the second phase of Mammary Involution. Importantly, at day 3 of Mammary Involution the Na-Pi type IIb co-transporter (Npt2b), a selective marker for active lactation in luminal lobular alveolar epithelium, was completely silenced in the WAP-Cre control and T beta RII(WKO)Rosa26R tissues. However, by day 7 of Involution the T beta RII(WKO)Rosa26R tissues had distended lobular alveoli and regained a robust Npt2b signal that was detected at the apical luminal surface. The Npt2b abundance and localization positively correlated with elevated WAP mRNA expression, suggesting that the distended alveoli were the result of an active lactation program rather than residual milk protein and lipid accumulation. In summary, the results suggest that an epithelial cell response to TGF-beta signaling regulates commitment to cell death and suppression of lactation during the second phase of Mammary Involution.
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TGF‐β promotes cell death and suppresses lactation during the second stage of Mammary Involution
Journal of cellular physiology, 2009Co-Authors: Brian Bierie, Agnieszka E. Gorska, Daniel G. Stover, Harold L. MosesAbstract:Transforming growth factor beta (TGF-beta) ligands are known to regulate virgin Mammary development and contribute to initiation of post-lactation Involution. However, the role for TGF-beta during the second phase of Mammary Involution has not been addressed. Previously, we have used an MMTV-Cre transgene to delete exon 2 from the Tgfbr2 gene in Mammary epithelium, however we observed a gradual loss of T beta RII deficient epithelial cells that precluded an accurate study of the role for TGF-beta signaling during Involution timepoints. Therefore, in order to determine the role for TGF-beta during the second phase of Mammary Involution we have now targeted T beta RII ablation within Mammary epithelium using the WAP-Cre transgene [T beta RII(WKO)Rosa26R]. Our results demonstrated that TGF-beta regulates commitment to cell death during the second phase of Mammary Involution. Importantly, at day 3 of Mammary Involution the Na-Pi type IIb co-transporter (Npt2b), a selective marker for active lactation in luminal lobular alveolar epithelium, was completely silenced in the WAP-Cre control and T beta RII(WKO)Rosa26R tissues. However, by day 7 of Involution the T beta RII(WKO)Rosa26R tissues had distended lobular alveoli and regained a robust Npt2b signal that was detected at the apical luminal surface. The Npt2b abundance and localization positively correlated with elevated WAP mRNA expression, suggesting that the distended alveoli were the result of an active lactation program rather than residual milk protein and lipid accumulation. In summary, the results suggest that an epithelial cell response to TGF-beta signaling regulates commitment to cell death and suppression of lactation during the second phase of Mammary Involution.
Virginia F. Borges - One of the best experts on this subject based on the ideXlab platform.
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Deciphering Pro-Lymphangiogenic Programs during Mammary Involution and Postpartum Breast Cancer.
Frontiers in oncology, 2016Co-Authors: Virginia F. Borges, Alan M. Elder, Traci R. LyonsAbstract:Postpartum breast cancers are a highly metastatic subset of young women’s breast cancers defined as breast cancers diagnosed in the postpartum period or within 5 years of last child-birth. Women diagnosed with postpartum breast cancer are nearly twice as likely to develop metastasis and to die from breast cancer when compared to nulliparous women. Additionally, epidemiological studies utilizing multiple cohorts also suggest that nearly half of all breast cancers in women aged
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deciphering pro lymphangiogenic programs during Mammary Involution and postpartum breast cancer
Frontiers in Oncology, 2016Co-Authors: Virginia F. Borges, Alan M. Elder, Traci R. LyonsAbstract:Postpartum breast cancers are a highly metastatic subset of young women’s breast cancers defined as breast cancers diagnosed in the postpartum period or within 5 years of last child-birth. Women diagnosed with postpartum breast cancer are nearly twice as likely to develop metastasis and to die from breast cancer when compared to nulliparous women. Additionally, epidemiological studies utilizing multiple cohorts also suggest that nearly half of all breast cancers in women aged <45 qualify as postpartum cases. Understanding the biology that underlies this increased risk for metastasis and death may lead to identification of targeted interventions that will benefit the large number of young women with breast cancer who fall into this subset. Preclinical mouse models of postpartum breast cancer have revealed that breast tumor cells become more aggressive if they are present during the normal physiologic process of postpartum Mammary gland Involution in mice. As Involution appears to be a period of lymphatic growth and remodeling, and human postpartum breast cancers have high peri-tumor lymphatic vessel density (LVD) and increased incidence of lymph node metastasis37,41, we propose that novel insight into is to be gained through the study of the biological mechanisms driving normal postpartum Mammary lymphangiogenesis as well as in the microenvironment of postpartum tumors.
Brian Bierie - One of the best experts on this subject based on the ideXlab platform.
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tgf β promotes cell death and suppresses lactation during the second stage of Mammary Involution
Journal of Cellular Physiology, 2009Co-Authors: Brian Bierie, Agnieszka E. Gorska, Daniel G. Stover, Harold L. MosesAbstract:Transforming growth factor beta (TGF-beta) ligands are known to regulate virgin Mammary development and contribute to initiation of post-lactation Involution. However, the role for TGF-beta during the second phase of Mammary Involution has not been addressed. Previously, we have used an MMTV-Cre transgene to delete exon 2 from the Tgfbr2 gene in Mammary epithelium, however we observed a gradual loss of T beta RII deficient epithelial cells that precluded an accurate study of the role for TGF-beta signaling during Involution timepoints. Therefore, in order to determine the role for TGF-beta during the second phase of Mammary Involution we have now targeted T beta RII ablation within Mammary epithelium using the WAP-Cre transgene [T beta RII(WKO)Rosa26R]. Our results demonstrated that TGF-beta regulates commitment to cell death during the second phase of Mammary Involution. Importantly, at day 3 of Mammary Involution the Na-Pi type IIb co-transporter (Npt2b), a selective marker for active lactation in luminal lobular alveolar epithelium, was completely silenced in the WAP-Cre control and T beta RII(WKO)Rosa26R tissues. However, by day 7 of Involution the T beta RII(WKO)Rosa26R tissues had distended lobular alveoli and regained a robust Npt2b signal that was detected at the apical luminal surface. The Npt2b abundance and localization positively correlated with elevated WAP mRNA expression, suggesting that the distended alveoli were the result of an active lactation program rather than residual milk protein and lipid accumulation. In summary, the results suggest that an epithelial cell response to TGF-beta signaling regulates commitment to cell death and suppression of lactation during the second phase of Mammary Involution.
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TGF‐β promotes cell death and suppresses lactation during the second stage of Mammary Involution
Journal of cellular physiology, 2009Co-Authors: Brian Bierie, Agnieszka E. Gorska, Daniel G. Stover, Harold L. MosesAbstract:Transforming growth factor beta (TGF-beta) ligands are known to regulate virgin Mammary development and contribute to initiation of post-lactation Involution. However, the role for TGF-beta during the second phase of Mammary Involution has not been addressed. Previously, we have used an MMTV-Cre transgene to delete exon 2 from the Tgfbr2 gene in Mammary epithelium, however we observed a gradual loss of T beta RII deficient epithelial cells that precluded an accurate study of the role for TGF-beta signaling during Involution timepoints. Therefore, in order to determine the role for TGF-beta during the second phase of Mammary Involution we have now targeted T beta RII ablation within Mammary epithelium using the WAP-Cre transgene [T beta RII(WKO)Rosa26R]. Our results demonstrated that TGF-beta regulates commitment to cell death during the second phase of Mammary Involution. Importantly, at day 3 of Mammary Involution the Na-Pi type IIb co-transporter (Npt2b), a selective marker for active lactation in luminal lobular alveolar epithelium, was completely silenced in the WAP-Cre control and T beta RII(WKO)Rosa26R tissues. However, by day 7 of Involution the T beta RII(WKO)Rosa26R tissues had distended lobular alveoli and regained a robust Npt2b signal that was detected at the apical luminal surface. The Npt2b abundance and localization positively correlated with elevated WAP mRNA expression, suggesting that the distended alveoli were the result of an active lactation program rather than residual milk protein and lipid accumulation. In summary, the results suggest that an epithelial cell response to TGF-beta signaling regulates commitment to cell death and suppression of lactation during the second phase of Mammary Involution.
David J. Flint - One of the best experts on this subject based on the ideXlab platform.
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Insulin-like growth factor binding protein-5 (IGFBP-5) potentially regulates programmed cell death and plasminogen activation in the Mammary gland.
Advances in experimental medicine and biology, 2000Co-Authors: Elizabeth Tonner, John Webster, Gordon J. Allan, Lulzim Shkreta, C. Bruce, A. Whitelaw, David J. FlintAbstract:This study aims to investigate the mechanism by which prolactin and GH interact to maintain Mammary epithelial cell function in the rat. IGF-I is an important survival factor for the Mammary gland and we have demonstrated that the effects of GH and prolactin involve IGF-I. GH acts by increasing IGF- I whilst prolactin acts by inhibiting the expression of IGFBP-5 from the Mammary epithelium. During Mammary Involution, when serum prolactin levels decline, IGFBP-5 expression is dramatically upregulated and it binds with high affinity to IGF-I preventing IGF-I interaction with the IGF-receptor and thus leading to epithelial cell apoptosis. We have identified a specific interaction of IGFBP-5 with αS2-casein. This milk protein has also been shown to bind plasminogen and its activator tissue-type plasminogen activator (tPA) leading to enhanced conversion of plasminogen to plasmin. Plasmin is an important initiator of re-modelling of the extracellular matrix during Mammary Involution. A potential interaction between the cell death and extracellular matrix remodelling is evident from the observation that IGFBP-5 binds to plasminogen activator inhibitor-I (PAI- 1). We thus hypothesized that IGFBP-5 could activate cell death by sequestration of IGF-I and activate plasminogen cleavage by sequestering PAI- 1. I in support of this hypothesis we have shown that both prolactin and GH inhibit tPA activity and plasminogen activation in the involuting Mammary gland. Our results suggest that GH and prolactin inhibit cell death and ECM remodelling via the IGF-axis and also indicate a novel role for the milk protein \( \alpha _{S_2 } \) in this process. We have now established lines of transgenic mice expressing IGFBP-5 on the β-lactoglobulin promoter to explore its function in greater detail.
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Control of Milk Secretion and Apoptosis DuringMammary Involution
Journal of Mammary Gland Biology and Neoplasia, 1999Co-Authors: Colin J. Wilde, Christopherh. Knight, David J. FlintAbstract:Lactation depends on regular suckling or milkingof the Mammary gland. Without this stimulus, milksecretion stops and Mammary Involution is induced.Involution caused by abrupt cessation of milk removal is characterized by de-differentiation andapoptosis of Mammary epithelial cells, the extent andtime course of the latter varying between species.Apoptosis is inhibited and milk secretion is restored by re-suckling, if milk stasis is of shortduration. Mammary Involution and apoptosis also occurduring weaning, even in concurrently-pregnant animalswhen the interval between lactations is restricted, suggesting that tissue remodeling is essentialfor subsequent lactation. Declining milk production inruminants after peak lactation is also associated with,and probably results from, net cell loss by apoptosis. Involution and apoptosis arecontrolled by changes in systemic galactopoietic hormonelevels, and by intra-Mammary mechanisms responsive tomilk removal. Milk stasis precipitated by litter removal or cessation of milking may involveintra-Mammary control related to physical distension ofthe epithelium. Local control of apoptosis in rodentsduring weaning, and after peak lactation in dairyanimals, may be due to the actions of milk-bornesurvival factors or their inhibitors, and can bemanipulated by frequency of milk removal.
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hormonal control of insulin like growth factor binding protein 5 production in the involuting Mammary gland of the rat
Endocrinology, 1997Co-Authors: Elizabeth Tonner, Michael C Barber, Maureen T Travers, Ann Logan, David J. FlintAbstract:We have demonstrated a 50-fold increase in the concentration of insulin-like growth factor-binding protein-5 (IGFBP-5) in milk after 2 days of Mammary Involution induced by removal of the suckling young. IGFBP-5 was identified by its immunoreactivity with an antiserum to IGFBP-5 and was shown by in situ hybridization to be synthesized by the secretory epithelial cells undergoing apoptosis. Smaller increases in IGFBP-2 and -4 messenger RNAs (mRNAs) were also evident, but neither protein could be detected on Western ligand blots of milk. Preliminary evidence failed to detect mRNAs for IGFBP-1, -3, or -6. The large increase in IGFBP-5 concentrations in milk from involuting Mammary glands was inhibited by 90% if the dams received concurrent PRL injections for 2 days, but was unaffected by GH, progesterone, corticosterone, or an antiserum to insulin-like growth factor I (IGF-I). In lactating rats allowed to continue nursing their young, 17β-estradiol failed to affect IGFBP-5 concentrations, whereas in animals ...
