Project/Area Number |
26293079
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Human pathology
|
Research Institution | Nara Medical University |
Principal Investigator |
Konishi Noboru 奈良県立医科大学, 医学部, 教授 (20145832)
|
Co-Investigator(Kenkyū-buntansha) |
藤本 清秀 奈良県立医科大学, 医学部, 教授 (50264867)
藤井 智美 奈良県立医科大学, 医学部, 講師 (50623477)
島田 啓司 奈良県立医科大学, 医学部, 研究員 (90336850)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
|
Keywords | 前立腺癌 / 癌始原細胞 / cancer progenitor cells / Syndecan-1 / heparanase / autophagy / TRAMPマウス / 人体病理学 / syndecan-1 / ヘパラナーゼ / 前立腺progenitor cells / IL-6 |
Outline of Final Research Achievements |
Heparanase-an enzyme that activates syndecan-is overexpressed in PIA lesions and contributes to the differentiation of basal cells to intermediate cells. Heparanase also suppressed the induction of autophagy by enhancing STAT3 phosphorylation in human prostatic epithelial cells at different passages by which carcinogenetic process could be executed in human prostate. Immunohistochemistry data for autophagy-related molecules, such as LC3, support the in vitro data. In the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model of prostate cancer, early intervention with a syndecan-1 inhibitor reduced the incidence of adenocarcinoma. Antibody for syndecan-1 produced in this study was immunoreactive, but not cytotoxic. Heparanase may play important roles in the neoplastic transformation of intermediate cells in response to regulation of autophagy, and thus indicate that heparanase may be a molecular target for prostate cancer therapy and chemoprevention.
|