The novel roles of c-Met and Lutheran in bladder cancer formation
碩士 === 國立成功大學 === 微生物及免疫學研究所 === 93 === Met, the hepatocyte growth factor (HGF) receptor, is a receptor tyrosine kinase (RTK), and plays an important role in regulating cellular proliferation, motility, and apoptosis. Previously studies indicated that HGF/Met signaling might play a critical role in...
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ndltd-TW-093NCKU53800142017-06-04T04:40:13Z http://ndltd.ncl.edu.tw/handle/83633726684800262504 The novel roles of c-Met and Lutheran in bladder cancer formation 探討c-Met及Lutheran在膀胱癌發展過程的新穎角色 Chen-Yun Yeh 葉承昀 碩士 國立成功大學 微生物及免疫學研究所 93 Met, the hepatocyte growth factor (HGF) receptor, is a receptor tyrosine kinase (RTK), and plays an important role in regulating cellular proliferation, motility, and apoptosis. Previously studies indicated that HGF/Met signaling might play a critical role in bladder carcinogenesis. To reveal the novel role of Met in the process of tumorigenesis, a NIH/3T3 derivate, NIH-Met5, with c-Met overexpression in an inducible way by tetracycline was established. We found that c-Met was highly auto-phosphorylated without HGF treatment when c-Met was overexpressed. Treatment of HGF could further enhance c-Met phosphorylation via a dose-dependent way. Utilizing microarray analysis, we found the gene expression profile of kinases Axl and PDGFR-���nare up-regulated. In bladder cancer cell lines, we also found that Axl and PDGFR-�� were up-regulated by HGF treatment. In immunohistochemistry analysis, cinical specimens demonstrated the co-expression of c-Met, Axl, and PDGFR-�� positively associated with aggressive biological indicators or tumor metastasis. In summary, we found two c-Met-regulated genes. The Lutheran glycoprotein (LU) is a basolateral antigen in diverse epithelial cells. In our previously studies, treatment of laminin-10 on NIH-Lu11, over-expressing LU cells, could promote anchorage-independent growth and enhance cell adhesion through activation of Erk/RhoA signaling pathway, and RhoA induced the stress fiber formation. We found that NIH-Lu11 could induce NF-kB activity after laminin-10 treatment and tumor formation in the BALB/c and immune deficiency NOD-SCID mice, suggesting the oncogenesity of LU. Two bladder cancer cell lines, J82 and TCCSUP, expressing high level of LU were utilized to study the function of LU. The adhesion feature was blocked by Erk/MAPK inhibitor PD98059, p38 inhibitor SB203580 and Rho GTPase inhibitor C3 exoenzyme treatment. In pull-down assay, we showed that RhoA activity was enhanced via Erk-mediated signaling pathway after laminin-10 treatment. After treating cytochalasin B, a stress fiber inhibitor, cell adhesion was suppressed; suggesting stress fiber was involved in adhesion ability. These results demonstrated that all of Erk/MAPK, p38 and RhoA molecular were involved in adhesion ability. In summary, we confirmed that Lu was an oncogene, and plays an important role in mediating the attachment of cancer cells to the extracellular matrix, correlating to the cancer progression. Hsiao-Sheng Liu 劉校生 2005 學位論文 ; thesis 67 en_US |
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碩士 === 國立成功大學 === 微生物及免疫學研究所 === 93 === Met, the hepatocyte growth factor (HGF) receptor, is a receptor tyrosine kinase (RTK), and plays an important role in regulating cellular proliferation, motility, and apoptosis. Previously studies indicated that HGF/Met signaling might play a critical role in bladder carcinogenesis. To reveal the novel role of Met in the process of tumorigenesis, a NIH/3T3 derivate, NIH-Met5, with c-Met overexpression in an inducible way by tetracycline was established. We found that c-Met was highly auto-phosphorylated without HGF treatment when c-Met was overexpressed. Treatment of HGF could further enhance c-Met phosphorylation via a dose-dependent way. Utilizing microarray analysis, we found the gene expression profile of kinases Axl and PDGFR-���nare up-regulated. In bladder cancer cell lines, we also found that Axl and PDGFR-�� were up-regulated by HGF treatment. In immunohistochemistry analysis, cinical specimens demonstrated the co-expression of c-Met, Axl, and PDGFR-�� positively associated with aggressive biological indicators or tumor metastasis. In summary, we found two c-Met-regulated genes.
The Lutheran glycoprotein (LU) is a basolateral antigen in diverse epithelial cells. In our previously studies, treatment of laminin-10 on NIH-Lu11, over-expressing LU cells, could promote anchorage-independent growth and enhance cell adhesion through activation of Erk/RhoA signaling pathway, and RhoA induced the stress fiber formation. We found that NIH-Lu11 could induce NF-kB activity after laminin-10 treatment and tumor formation in the BALB/c and immune deficiency NOD-SCID mice, suggesting the oncogenesity of LU. Two bladder cancer cell lines, J82 and TCCSUP, expressing high level of LU were utilized to study the function of LU. The adhesion feature was blocked by Erk/MAPK inhibitor PD98059, p38 inhibitor SB203580 and Rho GTPase inhibitor C3 exoenzyme treatment. In pull-down assay, we showed that RhoA activity was enhanced via Erk-mediated signaling pathway after laminin-10 treatment. After treating cytochalasin B, a stress fiber inhibitor, cell adhesion was suppressed; suggesting stress fiber was involved in adhesion ability. These results demonstrated that all of Erk/MAPK, p38 and RhoA molecular were involved in adhesion ability. In summary, we confirmed that Lu was an oncogene, and plays an important role in mediating the attachment of cancer cells to the extracellular matrix, correlating to the cancer progression.
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author2 |
Hsiao-Sheng Liu |
author_facet |
Hsiao-Sheng Liu Chen-Yun Yeh 葉承昀 |
author |
Chen-Yun Yeh 葉承昀 |
spellingShingle |
Chen-Yun Yeh 葉承昀 The novel roles of c-Met and Lutheran in bladder cancer formation |
author_sort |
Chen-Yun Yeh |
title |
The novel roles of c-Met and Lutheran in bladder cancer formation |
title_short |
The novel roles of c-Met and Lutheran in bladder cancer formation |
title_full |
The novel roles of c-Met and Lutheran in bladder cancer formation |
title_fullStr |
The novel roles of c-Met and Lutheran in bladder cancer formation |
title_full_unstemmed |
The novel roles of c-Met and Lutheran in bladder cancer formation |
title_sort |
novel roles of c-met and lutheran in bladder cancer formation |
publishDate |
2005 |
url |
http://ndltd.ncl.edu.tw/handle/83633726684800262504 |
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