The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Makoto Shibutani - One of the best experts on this subject based on the ideXlab platform.
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crosstalk between pten akt2 and tgfβ signaling involving egf receptor down regulation during the tumor Promotion Process from the early stage in a rat two stage hepatocarcinogenesis model
Cancer Science, 2009Co-Authors: Eriko Taniai, Masaomi Kawai, Yasuaki Dewa, Jihei Nishimura, Tomoaki Harada, Yukie Saegusa, Sayaka Matsumoto, Miwa Takahashi, Kunitoshi Mitsumori, Makoto ShibutaniAbstract:The present study investigated the involvement of signaling of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) and transforming growth factor-β (TGFβ) as well as receptor tyrosine kinases in the tumor Promotion Processes in a two-stage hepatocarcinogenesis model using male F344 rats. The cellular localization of related molecules was examined in liver cell foci expressing glutathione S-transferase placental form (GST-P) at the early stage of tumor Promotion by fenbendazole (FB), piperonyl butoxide, or thioacetamide. Distribution in the liver cell foci and neoplastic lesions positive for GST-P was also examined at the later stage of FB Promotion. In contrast to the initiation-alone cases, subpopulations of GST-P-positive foci induced by Promotion for 6 weeks, regardless of the promoting chemicals used, enhanced down-regulation of PTEN and up-regulation of phosphorylated (active) Akt2 and phosphorylated substrate(s) of Akt-kinase activity. Also, up-regulation of TGFβ receptor I and down-regulation of epidermal growth factor receptor (EGFR) were enhanced in the subpopulation of GST-P-positive foci in all promoted cases. A similar pattern of cellular distribution of these molecules was also observed in the neoplastic lesions at the late stage. These results suggest a crosstalk between Akt2 and TGFβ signaling that involves a mechanism requiring EGFR down-regulation during the entire tumor Promotion Process starting from the early stage. In particular, a shift in subcellular localization of phosphorylated substrate(s) of Akt from the cell membrane in liver cell foci to the cytoplasm in carcinomas was observed, suggesting an alteration of the function or activity of the corresponding molecule(s). (Cancer Sci 2009; 100: 813–820)
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Crosstalk between PTEN/Akt2 and TGFβ signaling involving EGF receptor down‐regulation during the tumor Promotion Process from the early stage in a rat two‐stage hepatocarcinogenesis model
Cancer Science, 2009Co-Authors: Eriko Taniai, Masaomi Kawai, Yasuaki Dewa, Jihei Nishimura, Tomoaki Harada, Yukie Saegusa, Sayaka Matsumoto, Miwa Takahashi, Kunitoshi Mitsumori, Makoto ShibutaniAbstract:The present study investigated the involvement of signaling of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) and transforming growth factor-β (TGFβ) as well as receptor tyrosine kinases in the tumor Promotion Processes in a two-stage hepatocarcinogenesis model using male F344 rats. The cellular localization of related molecules was examined in liver cell foci expressing glutathione S-transferase placental form (GST-P) at the early stage of tumor Promotion by fenbendazole (FB), piperonyl butoxide, or thioacetamide. Distribution in the liver cell foci and neoplastic lesions positive for GST-P was also examined at the later stage of FB Promotion. In contrast to the initiation-alone cases, subpopulations of GST-P-positive foci induced by Promotion for 6 weeks, regardless of the promoting chemicals used, enhanced down-regulation of PTEN and up-regulation of phosphorylated (active) Akt2 and phosphorylated substrate(s) of Akt-kinase activity. Also, up-regulation of TGFβ receptor I and down-regulation of epidermal growth factor receptor (EGFR) were enhanced in the subpopulation of GST-P-positive foci in all promoted cases. A similar pattern of cellular distribution of these molecules was also observed in the neoplastic lesions at the late stage. These results suggest a crosstalk between Akt2 and TGFβ signaling that involves a mechanism requiring EGFR down-regulation during the entire tumor Promotion Process starting from the early stage. In particular, a shift in subcellular localization of phosphorylated substrate(s) of Akt from the cell membrane in liver cell foci to the cytoplasm in carcinomas was observed, suggesting an alteration of the function or activity of the corresponding molecule(s). (Cancer Sci 2009; 100: 813–820)
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cellular distributions of molecules with altered expression specific to the tumor Promotion Process from the early stage in a rat two stage hepatocarcinogenesis model
Carcinogenesis, 2008Co-Authors: Miwa Takahashi, Makoto Shibutani, Kaoru Inoue, Hitoshi Fujimoto, Katsuhide Igarashi, Jun Kanno, Masao Hirose, Akiyoshi NishikawaAbstract:A global gene expression profiling specific to the early Process of tumor Promotion by fenbendazole (FB) or phenobarbital (PB) in a rat two-stage hepatocarcinogenesis model revealed 33 genes to show altered expression in common with both chemicals. The immunohistochemical distribution of transferrin receptor (Tfrc), nuclear receptor subfamily 0, group B, member 2 (Nr0b2) and minichromosome maintenance deficient 6 (MCM6), included in the altered expression profile, were therefore examined in FB- and PB-induced proliferative lesions at both early and late stages of tumor Promotion. In addition, immunoexpression of transforming growth factor β receptor (TGFβR) I, TGFβRII, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (pPTEN) was also examined. In the early stage, most hepatocellular foci positive for glutathione S-transferase placental form (GST-P) showed co-expression of TGFβRI and lack of PTEN and pPTEN, some GST-P-positive foci co-expressing Tfrc and Nr0b2. In the late stage, selective expression of TGFβRI, but not TGFβRII, was also observed in many adenomas and carcinomas consistently expressing GST-P. Nr0b2 was variably expressed in the proliferative lesions, irrespective of the carcinogenic stage. Like the GST-P-positive foci, adenomas and carcinomas consistently lacked PTEN and pPTEN. Expression of Tfrc and MCM6 was increased in parallel with the carcinogenic stage. In conclusion, loss of PTEN and dysregulation of transforming growth factor β signaling can be considered to be involved in rat hepatocarcinogenesis from early stages. Selective expression of Tfrc in proliferative lesions suggests an involvement of changes in iron homeostasis during the Process of tumor Promotion/progression driven by FB or PB.
Miwa Takahashi - One of the best experts on this subject based on the ideXlab platform.
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crosstalk between pten akt2 and tgfβ signaling involving egf receptor down regulation during the tumor Promotion Process from the early stage in a rat two stage hepatocarcinogenesis model
Cancer Science, 2009Co-Authors: Eriko Taniai, Masaomi Kawai, Yasuaki Dewa, Jihei Nishimura, Tomoaki Harada, Yukie Saegusa, Sayaka Matsumoto, Miwa Takahashi, Kunitoshi Mitsumori, Makoto ShibutaniAbstract:The present study investigated the involvement of signaling of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) and transforming growth factor-β (TGFβ) as well as receptor tyrosine kinases in the tumor Promotion Processes in a two-stage hepatocarcinogenesis model using male F344 rats. The cellular localization of related molecules was examined in liver cell foci expressing glutathione S-transferase placental form (GST-P) at the early stage of tumor Promotion by fenbendazole (FB), piperonyl butoxide, or thioacetamide. Distribution in the liver cell foci and neoplastic lesions positive for GST-P was also examined at the later stage of FB Promotion. In contrast to the initiation-alone cases, subpopulations of GST-P-positive foci induced by Promotion for 6 weeks, regardless of the promoting chemicals used, enhanced down-regulation of PTEN and up-regulation of phosphorylated (active) Akt2 and phosphorylated substrate(s) of Akt-kinase activity. Also, up-regulation of TGFβ receptor I and down-regulation of epidermal growth factor receptor (EGFR) were enhanced in the subpopulation of GST-P-positive foci in all promoted cases. A similar pattern of cellular distribution of these molecules was also observed in the neoplastic lesions at the late stage. These results suggest a crosstalk between Akt2 and TGFβ signaling that involves a mechanism requiring EGFR down-regulation during the entire tumor Promotion Process starting from the early stage. In particular, a shift in subcellular localization of phosphorylated substrate(s) of Akt from the cell membrane in liver cell foci to the cytoplasm in carcinomas was observed, suggesting an alteration of the function or activity of the corresponding molecule(s). (Cancer Sci 2009; 100: 813–820)
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Crosstalk between PTEN/Akt2 and TGFβ signaling involving EGF receptor down‐regulation during the tumor Promotion Process from the early stage in a rat two‐stage hepatocarcinogenesis model
Cancer Science, 2009Co-Authors: Eriko Taniai, Masaomi Kawai, Yasuaki Dewa, Jihei Nishimura, Tomoaki Harada, Yukie Saegusa, Sayaka Matsumoto, Miwa Takahashi, Kunitoshi Mitsumori, Makoto ShibutaniAbstract:The present study investigated the involvement of signaling of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) and transforming growth factor-β (TGFβ) as well as receptor tyrosine kinases in the tumor Promotion Processes in a two-stage hepatocarcinogenesis model using male F344 rats. The cellular localization of related molecules was examined in liver cell foci expressing glutathione S-transferase placental form (GST-P) at the early stage of tumor Promotion by fenbendazole (FB), piperonyl butoxide, or thioacetamide. Distribution in the liver cell foci and neoplastic lesions positive for GST-P was also examined at the later stage of FB Promotion. In contrast to the initiation-alone cases, subpopulations of GST-P-positive foci induced by Promotion for 6 weeks, regardless of the promoting chemicals used, enhanced down-regulation of PTEN and up-regulation of phosphorylated (active) Akt2 and phosphorylated substrate(s) of Akt-kinase activity. Also, up-regulation of TGFβ receptor I and down-regulation of epidermal growth factor receptor (EGFR) were enhanced in the subpopulation of GST-P-positive foci in all promoted cases. A similar pattern of cellular distribution of these molecules was also observed in the neoplastic lesions at the late stage. These results suggest a crosstalk between Akt2 and TGFβ signaling that involves a mechanism requiring EGFR down-regulation during the entire tumor Promotion Process starting from the early stage. In particular, a shift in subcellular localization of phosphorylated substrate(s) of Akt from the cell membrane in liver cell foci to the cytoplasm in carcinomas was observed, suggesting an alteration of the function or activity of the corresponding molecule(s). (Cancer Sci 2009; 100: 813–820)
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cellular distributions of molecules with altered expression specific to the tumor Promotion Process from the early stage in a rat two stage hepatocarcinogenesis model
Carcinogenesis, 2008Co-Authors: Miwa Takahashi, Makoto Shibutani, Kaoru Inoue, Hitoshi Fujimoto, Katsuhide Igarashi, Jun Kanno, Masao Hirose, Akiyoshi NishikawaAbstract:A global gene expression profiling specific to the early Process of tumor Promotion by fenbendazole (FB) or phenobarbital (PB) in a rat two-stage hepatocarcinogenesis model revealed 33 genes to show altered expression in common with both chemicals. The immunohistochemical distribution of transferrin receptor (Tfrc), nuclear receptor subfamily 0, group B, member 2 (Nr0b2) and minichromosome maintenance deficient 6 (MCM6), included in the altered expression profile, were therefore examined in FB- and PB-induced proliferative lesions at both early and late stages of tumor Promotion. In addition, immunoexpression of transforming growth factor β receptor (TGFβR) I, TGFβRII, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (pPTEN) was also examined. In the early stage, most hepatocellular foci positive for glutathione S-transferase placental form (GST-P) showed co-expression of TGFβRI and lack of PTEN and pPTEN, some GST-P-positive foci co-expressing Tfrc and Nr0b2. In the late stage, selective expression of TGFβRI, but not TGFβRII, was also observed in many adenomas and carcinomas consistently expressing GST-P. Nr0b2 was variably expressed in the proliferative lesions, irrespective of the carcinogenic stage. Like the GST-P-positive foci, adenomas and carcinomas consistently lacked PTEN and pPTEN. Expression of Tfrc and MCM6 was increased in parallel with the carcinogenic stage. In conclusion, loss of PTEN and dysregulation of transforming growth factor β signaling can be considered to be involved in rat hepatocarcinogenesis from early stages. Selective expression of Tfrc in proliferative lesions suggests an involvement of changes in iron homeostasis during the Process of tumor Promotion/progression driven by FB or PB.
Eriko Taniai - One of the best experts on this subject based on the ideXlab platform.
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crosstalk between pten akt2 and tgfβ signaling involving egf receptor down regulation during the tumor Promotion Process from the early stage in a rat two stage hepatocarcinogenesis model
Cancer Science, 2009Co-Authors: Eriko Taniai, Masaomi Kawai, Yasuaki Dewa, Jihei Nishimura, Tomoaki Harada, Yukie Saegusa, Sayaka Matsumoto, Miwa Takahashi, Kunitoshi Mitsumori, Makoto ShibutaniAbstract:The present study investigated the involvement of signaling of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) and transforming growth factor-β (TGFβ) as well as receptor tyrosine kinases in the tumor Promotion Processes in a two-stage hepatocarcinogenesis model using male F344 rats. The cellular localization of related molecules was examined in liver cell foci expressing glutathione S-transferase placental form (GST-P) at the early stage of tumor Promotion by fenbendazole (FB), piperonyl butoxide, or thioacetamide. Distribution in the liver cell foci and neoplastic lesions positive for GST-P was also examined at the later stage of FB Promotion. In contrast to the initiation-alone cases, subpopulations of GST-P-positive foci induced by Promotion for 6 weeks, regardless of the promoting chemicals used, enhanced down-regulation of PTEN and up-regulation of phosphorylated (active) Akt2 and phosphorylated substrate(s) of Akt-kinase activity. Also, up-regulation of TGFβ receptor I and down-regulation of epidermal growth factor receptor (EGFR) were enhanced in the subpopulation of GST-P-positive foci in all promoted cases. A similar pattern of cellular distribution of these molecules was also observed in the neoplastic lesions at the late stage. These results suggest a crosstalk between Akt2 and TGFβ signaling that involves a mechanism requiring EGFR down-regulation during the entire tumor Promotion Process starting from the early stage. In particular, a shift in subcellular localization of phosphorylated substrate(s) of Akt from the cell membrane in liver cell foci to the cytoplasm in carcinomas was observed, suggesting an alteration of the function or activity of the corresponding molecule(s). (Cancer Sci 2009; 100: 813–820)
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Crosstalk between PTEN/Akt2 and TGFβ signaling involving EGF receptor down‐regulation during the tumor Promotion Process from the early stage in a rat two‐stage hepatocarcinogenesis model
Cancer Science, 2009Co-Authors: Eriko Taniai, Masaomi Kawai, Yasuaki Dewa, Jihei Nishimura, Tomoaki Harada, Yukie Saegusa, Sayaka Matsumoto, Miwa Takahashi, Kunitoshi Mitsumori, Makoto ShibutaniAbstract:The present study investigated the involvement of signaling of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) and transforming growth factor-β (TGFβ) as well as receptor tyrosine kinases in the tumor Promotion Processes in a two-stage hepatocarcinogenesis model using male F344 rats. The cellular localization of related molecules was examined in liver cell foci expressing glutathione S-transferase placental form (GST-P) at the early stage of tumor Promotion by fenbendazole (FB), piperonyl butoxide, or thioacetamide. Distribution in the liver cell foci and neoplastic lesions positive for GST-P was also examined at the later stage of FB Promotion. In contrast to the initiation-alone cases, subpopulations of GST-P-positive foci induced by Promotion for 6 weeks, regardless of the promoting chemicals used, enhanced down-regulation of PTEN and up-regulation of phosphorylated (active) Akt2 and phosphorylated substrate(s) of Akt-kinase activity. Also, up-regulation of TGFβ receptor I and down-regulation of epidermal growth factor receptor (EGFR) were enhanced in the subpopulation of GST-P-positive foci in all promoted cases. A similar pattern of cellular distribution of these molecules was also observed in the neoplastic lesions at the late stage. These results suggest a crosstalk between Akt2 and TGFβ signaling that involves a mechanism requiring EGFR down-regulation during the entire tumor Promotion Process starting from the early stage. In particular, a shift in subcellular localization of phosphorylated substrate(s) of Akt from the cell membrane in liver cell foci to the cytoplasm in carcinomas was observed, suggesting an alteration of the function or activity of the corresponding molecule(s). (Cancer Sci 2009; 100: 813–820)
Akiyoshi Nishikawa - One of the best experts on this subject based on the ideXlab platform.
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cellular distributions of molecules with altered expression specific to the tumor Promotion Process from the early stage in a rat two stage hepatocarcinogenesis model
Carcinogenesis, 2008Co-Authors: Miwa Takahashi, Makoto Shibutani, Kaoru Inoue, Hitoshi Fujimoto, Katsuhide Igarashi, Jun Kanno, Masao Hirose, Akiyoshi NishikawaAbstract:A global gene expression profiling specific to the early Process of tumor Promotion by fenbendazole (FB) or phenobarbital (PB) in a rat two-stage hepatocarcinogenesis model revealed 33 genes to show altered expression in common with both chemicals. The immunohistochemical distribution of transferrin receptor (Tfrc), nuclear receptor subfamily 0, group B, member 2 (Nr0b2) and minichromosome maintenance deficient 6 (MCM6), included in the altered expression profile, were therefore examined in FB- and PB-induced proliferative lesions at both early and late stages of tumor Promotion. In addition, immunoexpression of transforming growth factor β receptor (TGFβR) I, TGFβRII, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (pPTEN) was also examined. In the early stage, most hepatocellular foci positive for glutathione S-transferase placental form (GST-P) showed co-expression of TGFβRI and lack of PTEN and pPTEN, some GST-P-positive foci co-expressing Tfrc and Nr0b2. In the late stage, selective expression of TGFβRI, but not TGFβRII, was also observed in many adenomas and carcinomas consistently expressing GST-P. Nr0b2 was variably expressed in the proliferative lesions, irrespective of the carcinogenic stage. Like the GST-P-positive foci, adenomas and carcinomas consistently lacked PTEN and pPTEN. Expression of Tfrc and MCM6 was increased in parallel with the carcinogenic stage. In conclusion, loss of PTEN and dysregulation of transforming growth factor β signaling can be considered to be involved in rat hepatocarcinogenesis from early stages. Selective expression of Tfrc in proliferative lesions suggests an involvement of changes in iron homeostasis during the Process of tumor Promotion/progression driven by FB or PB.
Kunitoshi Mitsumori - One of the best experts on this subject based on the ideXlab platform.
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crosstalk between pten akt2 and tgfβ signaling involving egf receptor down regulation during the tumor Promotion Process from the early stage in a rat two stage hepatocarcinogenesis model
Cancer Science, 2009Co-Authors: Eriko Taniai, Masaomi Kawai, Yasuaki Dewa, Jihei Nishimura, Tomoaki Harada, Yukie Saegusa, Sayaka Matsumoto, Miwa Takahashi, Kunitoshi Mitsumori, Makoto ShibutaniAbstract:The present study investigated the involvement of signaling of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) and transforming growth factor-β (TGFβ) as well as receptor tyrosine kinases in the tumor Promotion Processes in a two-stage hepatocarcinogenesis model using male F344 rats. The cellular localization of related molecules was examined in liver cell foci expressing glutathione S-transferase placental form (GST-P) at the early stage of tumor Promotion by fenbendazole (FB), piperonyl butoxide, or thioacetamide. Distribution in the liver cell foci and neoplastic lesions positive for GST-P was also examined at the later stage of FB Promotion. In contrast to the initiation-alone cases, subpopulations of GST-P-positive foci induced by Promotion for 6 weeks, regardless of the promoting chemicals used, enhanced down-regulation of PTEN and up-regulation of phosphorylated (active) Akt2 and phosphorylated substrate(s) of Akt-kinase activity. Also, up-regulation of TGFβ receptor I and down-regulation of epidermal growth factor receptor (EGFR) were enhanced in the subpopulation of GST-P-positive foci in all promoted cases. A similar pattern of cellular distribution of these molecules was also observed in the neoplastic lesions at the late stage. These results suggest a crosstalk between Akt2 and TGFβ signaling that involves a mechanism requiring EGFR down-regulation during the entire tumor Promotion Process starting from the early stage. In particular, a shift in subcellular localization of phosphorylated substrate(s) of Akt from the cell membrane in liver cell foci to the cytoplasm in carcinomas was observed, suggesting an alteration of the function or activity of the corresponding molecule(s). (Cancer Sci 2009; 100: 813–820)
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Crosstalk between PTEN/Akt2 and TGFβ signaling involving EGF receptor down‐regulation during the tumor Promotion Process from the early stage in a rat two‐stage hepatocarcinogenesis model
Cancer Science, 2009Co-Authors: Eriko Taniai, Masaomi Kawai, Yasuaki Dewa, Jihei Nishimura, Tomoaki Harada, Yukie Saegusa, Sayaka Matsumoto, Miwa Takahashi, Kunitoshi Mitsumori, Makoto ShibutaniAbstract:The present study investigated the involvement of signaling of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) and transforming growth factor-β (TGFβ) as well as receptor tyrosine kinases in the tumor Promotion Processes in a two-stage hepatocarcinogenesis model using male F344 rats. The cellular localization of related molecules was examined in liver cell foci expressing glutathione S-transferase placental form (GST-P) at the early stage of tumor Promotion by fenbendazole (FB), piperonyl butoxide, or thioacetamide. Distribution in the liver cell foci and neoplastic lesions positive for GST-P was also examined at the later stage of FB Promotion. In contrast to the initiation-alone cases, subpopulations of GST-P-positive foci induced by Promotion for 6 weeks, regardless of the promoting chemicals used, enhanced down-regulation of PTEN and up-regulation of phosphorylated (active) Akt2 and phosphorylated substrate(s) of Akt-kinase activity. Also, up-regulation of TGFβ receptor I and down-regulation of epidermal growth factor receptor (EGFR) were enhanced in the subpopulation of GST-P-positive foci in all promoted cases. A similar pattern of cellular distribution of these molecules was also observed in the neoplastic lesions at the late stage. These results suggest a crosstalk between Akt2 and TGFβ signaling that involves a mechanism requiring EGFR down-regulation during the entire tumor Promotion Process starting from the early stage. In particular, a shift in subcellular localization of phosphorylated substrate(s) of Akt from the cell membrane in liver cell foci to the cytoplasm in carcinomas was observed, suggesting an alteration of the function or activity of the corresponding molecule(s). (Cancer Sci 2009; 100: 813–820)
