Genomic Imprinting of the M6P/IGF2 Receptor: A Novel Breast Cancer Susceptibility Mechanism
Abstract
The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) gene encodes for a receptor that plays a critical role in regulating the bioavailability of extracellular proteolytic enzymes and growth factors known to be involved in carcinogenesis. Our recent findings indicate that the M6P/IGF2R also functions as a tumor suppressor gene in liver, breast, and lung cancer. We hypothesize that M6P/IGF2R gene inactivation, by the novel mechanism of genomic imprinting, results in a non-Mendelian inherited predisposition to breast cancer. We have determined that the frequency of monoallelic M6P/IGF2R expression in breast cancer patients is higher than that of age-matched controls and are currently investigating the mechanism underlying the monoallelic expression in these patients. Based on exciting new information we have obtained for Wilms' tumors, we are presently testing the hypothesis that deficiency in M6P/IGF2R expression in these breast cancer patients is due to mutations in intron 10 of the M6P/IGF2R gene. These results would demonstrate a novel mechanism for the induction of breast carcinogenesis due to inactivation of the M6P/IGF2R gene through a post-transcriptional mechanism. Future studies will be directed at determining whether this is a result of spontaneous mutation or rather represents a heritable trait, which may be useful as a predictive and/or prognostic indicator of breast cancer susceptibility.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA379346
Entities
People
- Randy L. Jirtle
Organizations
- Duke University Hospital