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

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591337
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Nagoya 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
• Keywords: SHPS-1 / Breast Cancer

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.