Research for esophageal carcinogenesis and proliferation, by characterization of cancer stem cells and analysis of the inactivation mechanism for suppressor genes in normal esophageal epithelial cells.
| Project/Area Number |
17390363
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Hyogo College of Medicine (2006)
Kyoto University (2005) |
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Principal Investigator |
SHIMADA Yutaka Hyogo College of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 講師 (30216072)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Go Kyoto University, Graduate School of medicine, Assistant Professor, 医学研究科, 講師 (50293866)
ITAMI Atsushi Kyoto University, Graduate School of medicine, Research Associate, 医学研究科, 助手 (40362511)
加賀野井 純一 京都大学, 医学研究科, 助手 (60378619)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Cancer stem cell / Normal esophageal epithelial cell / p75NTR / ABCG2 / Hedgeho / Gli-1 / NGF / FHIT / Hedgehog / 癌抑制遺伝子 |
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| Research Abstract |
p75NTR
p75NTR was expressed in all examined esophageal squamous cell carcinoma (ESCC) and the mean proportion of the p75NTR-positive fraction was 30.1%. The size of p75NTR-positive colonies was larger than that of p75NTR-negative colonies (p<0.0001). Down regulation of p75NTR expression by SiRNA resulted in marked growth inhibition with induction of apoptosis. Our findings suggest that p75NTR was expressed in a small number of cells in ESCC cell lines and p75NTR is necessary for survival and maintenance of ESCC tumors.
ABCG2
ABCG2 expression was detectable in 61% of patients and the proportion of ABCG2 positive cells was variable (0% to 100%). The presence of ABCG2 positive cells in the tumor was revealed to be an independent prognostic factor along with the extent of the primary tumor and positive lymph node metastasis in multivariate analysis. Our data suggests that ABCG2 plays an underlying role in malignant characteristics of ESCC.
Glil
Cell proliferation and migration were significantly inhibited by Cyclopamine in the cell lines that expressed all Hedgehog (Hh) pathway molecules, while cell proliferation was not affected in the cell lines lacking Shh and Gli-1 expression. SiRNA target for Gli-1 inhibited the cell growth of ESCC cells.
FHIT
Nicotine induced methylation of the FHIT gene and attenuated Fhit protein, associated with DNMT3a expression in normal esophageal epithelial cells (HEEC). Furthermore, re-expression of Fhit protein of HEECs was found after cessation of moderate- to long-term exposure to nicotine.
NGF
NGF overexpression was associated with lymph node metastasis, distant metastasis, higher TNM stage, poorer tumour differentiation and poorer survival of esophageal cancer patients. The motility of HSA/c, one of the ESCC cell lines overexpressing NGF, was significantly decreased by either neutralizing NGF antibody, an inhibitor of TrkA, or NGF-small interfering RNA in transwell migration assay.
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Report
(3 results)
Research Products
(34 results)
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[Journal Article] The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53 Yosuke Hashimoto, Tetsuo Ito, Harutaka Inoue2005
Author(s)
Hiroaki Higashitsuji, Hisako Higashitsuji, Katsuhiko Itoh, Toshiharu Sakurai, Toshikazu Nagao, Haruhiko Sumitomo, Tomoko Masuda, Simon Dawson, Yutaka Shimada, R. John Mayer, Jun Fujita.
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Journal Title
Cancer Cell 8・1
Pages: 75-87
Description
「研究成果報告書概要(欧文)」より
Related Report
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