Accession Number:

ADA394915

Title:

IGF Regulation of Cell Adhesion in Breast Cancer

Descriptive Note:

Annual rept. 1 Jul 1999-30 Jun 2000

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC

Personal Author(s):

Report Date:

2000-07-01

Pagination or Media Count:

13.0

Abstract:

Studies with gene knockout mice have demonstrated M6PIGF2R is an inhibitor of IGF2-dependent embryonic growth. Tumor-associated M6PIGF2R mutations that disrupt IGF2 binding have been described suggesting that the IGF2 antagonist action of M6PIGF2R may also play a role suppressing tumorigenesis. To investigate the role of M6PIGF2R as an IGF2 antagonist in breast cancer, M6PIGF2R was overexpressed in IGF2-sensitive MCF7 cells. Recombinant IGF1 - and IGF2-dependent proliferation was compared between control transfected cells, cells constitutively overexpressing wildtype M6PIGF2R and cells overexpressing an IGF2-binding or an M6P-binding defective mutant. Despite 5- to 10-fold overexpression of wildtype M6PIGF2R, IGF2-dependent growth in either monolayer or in suspension culture was unaffected. To confirm this unanticipated negative result, MCF7 cell clones engineered to overexpress wildtype M6PIGF2R under the control of a doxycycline inducible promoter were utilized. Ten- to 15-fold induction of M6PIGF2R expression with doxycycline resulted in no change of growth rate for cells in the presence of IGF2 when compared with control cells. It has previously been demonstrated that affinity of IGF2 for M6PIGF2R suppresses autocrine IGF2 activity Ellis, M. J. C. et a., Mol Endo 10286-297, 1996. These data therefore suggests that M6PIGF2R may operate to inhibit autocrine IGF2 within the secretory pathway but not efficiently suppress the action of IGF2 after it has been released from the cell.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE