Isolation of a Breast Cancer Tumor Suppressor Gene from Chromosome 3p
Abstract
Loss of tumor suppressor genes (TSGs) represent critical molecular events in the development and progression of breast cancer. Based on loss of heterozygosity (LOH) studies as well as direct cytogenetic studies of breast tumors, one or more TSGs likely resides on the short arm of chromosome 3 (3p) and appears to be involved in nearly 50% of breast cancers. Four distinct regions within 3p PL2, PL4, P2L (PROXIMAL) AND P2L (DISTAL) undergo recurrent deletions in human carcinomas and are the most likely sites for a breast cancer TSG. We demonstrated recurrent homozygous deletion or rearrangement in breast cancer cell lines involving 3pl4. A set of DNA clones spanning the critical region has been sequenced revealing several potential gene coding segments, some of which we now know are expressed in breast tumors. YACs containing the critical region have been modified with the Neomycin resistance gene for selective retention in mammalian cells. Introduction of the YAC into a murine fibrosarcoma cell line appears to inhibit its tumorigenicity, supporting the hypothesis that a tumor suppressor gene resides in the critical region. Evaluation of other regions for involvement in breast cancer as originally proposed using deletion detection, DNA sequence analysis, gene isolation and expression assays, is ongoing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADB233754
Entities
People
- Harry A. Drabkin
Organizations
- University of Colorado Boulder