Genes Altered by Intracisternal A Particles in Mouse Mammary Tumorigenesis.
Abstract
Retrotransposable elements comprise as much as 10-15% of mammalian genomes. Several of these elements possess the ability to relocate within the host's genome and thereby constitute a mechanism for genetic mutation leading to disease. Mouse mammary carcinomas of various etiologies show upregulation of two classes of retrotransposable elements, intracisternal a particles (IAPs) and murine viral leukemia elements (MuLVs). Expression of MuLVs has lead to the appearance of novel restriction fragments associated with the ecotropic MuLV in D2 HANs and several D2 tumors from BALB/c mice. Cloning flanking sequences to several integration sites and genetic mapping of a subset has suggested integration events have occurred in the D2 HANs and tumors. Characterization of one integration site, EN31, on chromosome 6 in the mouse, has identified a 140 kDa G-protein activating protein (GAP) for the small G-protein Rho. The RhoGAP was overexpressed in D2 HANs and tumors, D1 non-transformed and transformed cell lines, and fC3H mammary carcinomas. Expression of p14mRhoGAP in DMBA-induced primary mouse mammary carcinomas was reduced suggesting a role in ras dependent tumorigenesis. p140mRhoGAP was expressed most abundantly in the brain and in the developing nervous system. The pl40mRhoGAP was localized to the cytoplasm adjacent to the plasma membrane and was inhibitory to actin stress fiber formation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA377186
Entities
People
- Michael R. Crowley
Organizations
- Health Research, Incorporated