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The Research and Development of Gene Therapy for Breast Cancer by Src Signal Tiansduction Pathways

Research Project

Project/Area Number 15591337
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionNagoya University

Principal Investigator

ODA Koji  Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (30311715)

Co-Investigator(Kenkyū-buntansha) NIMURA Yuji  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80126888)
NAGINO Masato  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20237564)
ARAI Toshiyuki  Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (80335041)
HAMAGUCHI Michinari  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90135351)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsSHPS-1 / Breast Cancer / 遺伝子治療 / 接着分子
Research Abstract

Background : Src homology 2 domain-containing protein tyrosine phosphatase(SHP) substrate-1(SHPS-1 TS also known as p84,BIT, and SIRP) is a heterophilic adhesive membrane protein involved in receptor tyrosine kinase signaling that is expressed widely in the mammalian central nervous system, immune system and other tissues. The function of SHPS-1 is to control cell migration and spreading.
We studied the SHPS-1 cellular localization and its significance in relation to clinicopathological features including prognosis.
Design : Five cell lines and 63 specimens of breast carcinomas were examined to evaluate SHPS-1 expression and cellular localization by immunohistochemistry and western blotting. The monoclonal antibodies used was SHPS-1 (rabbit polyclonal antibody, Neomarkers). The clinicopathological factors studied were age, staging, tumor type, histological grade and mitotic index(MI). Overall survival and diseases-free survival were evaluated using the Kaplan-Meier method.
Result : We detected 100-kDa proteins in tissue samples and cell lines by Western blotting analysis. In normal epithelium, there was a membranous expression. In breast carcinomas, 22 cases (35%) showed cytoplasmic positivity (c+), whereas 4 leases (65%) were negative (c-), There was no difference in age, staging, type between c(+) and c(-). There was a statistically significant correlation between SHPS-1 expression and histological grade : 21cases (95%) of c(+) were G2-G3 tumors (P<0.05). The MI for c(+) cases(1.86±1.6) was significantly higher than that for C(-)(0.71±0.56). The cases with c(+) had poor overall and diseases-free survival rates than c(-)(P=0.044 and P=0.015,respectively).
Conclusion : It was suggested that cytoplasmic expression of SHPS-1 could be associated with gene mutation. SHPS-1 could be the logical candidate for gene therapy.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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