IGF Regulation of Cell Adhesion in Breast Cancer
Abstract
Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) has been identified as a putative tumor suppressor gene in both breast and liver cancers due to identification of loss of an allele at the M6P/IGF2R gene locus accompanied by somatic mutations in the remaining allele. Loss of M6P/IGF2R function is potentially complex because the receptor has a number of physiological roles including: 1) trafficking of mannose 6- phosphorylated lysosomal enzymes to endosomal compartments; 2) playing a role in proteolytic activation of transforming growth factor beta, a negative growth regulator and; targeting the potent mitogen IGF2 for degradation. Although genetic evidence is strong, there is no direct evidence to support the hypothesis that M6P/IGF2R is a tumor suppressor. In this investigation, transfection studies demonstrated that cells overexpressing wildtype (wt) M6P/IGF2R or a mutant deficient in M6P protein binding M6PdefR, showed reduced IGF2-stimulated growth when compared to cells transfected with a negative control or a mutant M6P/IGF2R unable to bind IGF2 (IGF2defR). Further, when IGF1 - and IGF2-stimulated growth were compared, only IGF2-stimulated growth was suppressed in cells overexpressing wt M6P/IGF2R or M6PdefR, suggesting that M6P/IGF2, as an IGF2 antagonist, is important in tumor suppression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA373932
Entities
People
- Stacey Da Costa
Organizations
- Georgetown University