Genetic Determinants of Inflammatory Breast Cancer
Abstract
Primary inflammatory breast cancer (IBC) accounts for approximately 6% of new breast cancers annually. We hypothesized that a limited number of concordant genetic alterations give rise to the unioue aggressive inflammatory phenotype of IBC. While working on the genetic determinants underlying the IBC phenotype, we found concordant and consistent alterations of two genes, RhoC GTPase and a novel IGF-binding protein (IGF-BP), in patients with IBC. RhoC was overexpressed in 90% of IBC samples examined compared to 30% of stage matched non-IBO tumors. LIBC was lost in 80% of the IBC samples and only 20% of non-IBC samples examined. Since RhoC and LIBC appear to act in concert in IBC, coupled to the preliminary evidence from other laboratories of genes from these families playing a role in pancreatic cancer (another highly aggressive adenocarcinoma), they are excellent candidate genes to begin to probe the genetic basis of the aggressive phenotype in IBC. We hypothesize that the phenotype of IBC is due to alterations in expression of RhoC and IGF-BP early in tumorigenesis. We will elucidate the signaling pathway downstream from RhoC CTPase and attempt to determine what effect RhoC and LIBC have on cellular motility and invasion.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA425765
Entities
People
- Sofia D Merajver
Organizations
- University of Michigan