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1997 Fiscal Year Final Research Report Summary

The expression of macrophage colony-stimulating factor and c-fms in the human endometrial and ovarian cancer and its metastatic potential

Research Project

Project/Area Number 07671819
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionSaitama Medical School

Principal Investigator

TAKEDA Satoru  Saitama Medical School, Associate Professor, 医学部, 助教授 (20143456)

Co-Investigator(Kenkyū-buntansha) TAKAGI Akiyoshi  Saitama Medical School, 医学部, 助手 (80226745)
Project Period (FY) 1995 – 1997
Keywordsendometrial cancer / ovarian cancer / M-CSF / c-fms / apoptosis / TNF-alpha / c-AMP
Research Abstract

Previously we found that the Ishikawa endometrial cancer cell line expresses macrophage colony-stimulating factor (M-CSF) and c-fms transcripts and that its proliferation is enhanced by the addition of recombinant M-CSF.Using retroviral infections to introduce and express exogenous c-fms genes in Ishikawa cells we also demonstrate proliferation to be partially inhibited by a dominant negative, mutant c-fms gene, yet enhanced approximately 3-fold by a normal c-fms gene, under conditions in which the only source of M-CSF was that produced by the cells. The data provide evidence for the existence of an active M-CSF/receptor loop in these endometrial cancer cells and suggests the possibility of such activity in tumors of the endometrium and ovary that aberrantly express M-CSF and c-fms genes.
TNF-alpha, LPS and c-AMP elevating agents such as foskolin, cholera toxin, 8-brom-c-AMP,dibutyryl-c-AMP,and IBMX,inhibited Ishikawa cell growth dosedependently, whereas M-CSF levels in medium were increased by these agents. Phorbol ester, TPA stimulated cell proliferation though protein kinase C pathway. We also demonstrated that TNF-alpha receptor antibody, specifically activating 55kDa TNF-alpha receptor, and TNF-alpha analogue, binding to 55kDa TNF-alpha receptor, induced apoptosis in Ishikawa and ovarian cancer cell lines, using TUNEL method and flow cytomtry.
TNF-alpha, LPS and c-AMP elevating agents inhibited cell proliferation in Ishikawa cells and ovarian cancer cells as well as in macrophage cell lines. It remains to be establishes whether these treatments caused a decrease in the expession of c-fms, and hence diminished sensitivity to M-CSF,despite the fact that the production of M-CSF was stimulated by these agents.

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Published: 1999-03-16  

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