IGF Regulation of Cell Adhesion in Breast Cancer
Abstract
Studies with gene knockout mice have demonstrated M6P/IGF2R is an inhibitor of IGF2-dependent embryonic growth. Tumor-associated M6P/IGF2R mutations that disrupt IGF2 binding have been described suggesting that the IGF2 antagonist action of M6P/IGF2R may also play a role suppressing tumorigenesis. To investigate the role of M6P/IGF2R as an IGF2 antagonist in breast cancer, M6P/IGF2R was overexpressed in IGF2-sensitive MCF7 cells. Recombinant IGF1 - and IGF2-dependent proliferation was compared between control transfected cells, cells constitutively overexpressing wildtype M6P/IGF2R and cells overexpressing an IGF2-binding or an M6P-binding defective mutant. Despite 5- to 10-fold overexpression of wildtype M6P/IGF2R, 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 M6P/IGF2R under the control of a doxycycline inducible promoter were utilized. Ten- to 15-fold induction of M6P/IGF2R 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 M6P/IGF2R suppresses autocrine IGF2 activity (Ellis, M. J. C. et a!., Mol Endo 10:286-297, 1996). These data therefore suggests that M6P/IGF2R 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA394915
Entities
People
- Stacey Dacosta
Organizations
- Georgetown University