IGF Regulation of Cell Adhesion in Breast Cancer
Abstract
Studies with gene knockout mice have demonstrated that M6P/IGF2R is an inhibitor of IGF2-dependent embryonic growth. Tumor- associated M6P/IGF2R mutations that may disrupt IGF2 binding have been described suggesting that the IGF2 antagonist action of M6P/IGF2R may also play a role in suppressing tumorigenesis. To investigate the role of M6P/IGF2R as an IGF2 antagonist in breast cancer, M6P/IGF2R was overexpressed in MCF7 cells. Despite overexpression of wildtype or binding defective mutant M6P/IGF2R, IGF2-dependent growth in either monolayer or in suspension culture was unaffected. MCF7 cell clones were also engineered to inducibly overexpress wildtype M6P/IGF2R (iwt1 cells). Despite 10-fold induction of M6P/IGF2R expression, IGF2-dependent growth and insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation were unaltered when compared with control cells. We had previously demonstrated that affinity of IGF2 for M6P/IGF2R suppresses autocrine IGF2 activity. These data led us to hypothesize that M6P/IGF2R may operate to inhibit autocrine IGF2 but not efficiently suppress exogenous IGF2 action. We therefore transfected iwt1 cells to constitutively express IGF2. We were unable to detect any effect of M6P/IGF2R overexpression on apoptosis or IRS-i phosphorylation signaling but could demonstrate antagonism of autocrine IGF2-dependent growth in monolayer culture. Although the functional evidence is insufficient to make the case that M6P/IGF2R is a tumor suppress or, the genetic evidence is compelling and justifies further experiments in various model systems.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396449
Entities
People
- Stacey Dacosta
Organizations
- Georgetown University