Functional Analysis of a Novel Transcription Factor That is Amplified and Overexpressed in Breast Cancers
Abstract
The candidate oncogene ZNF217 was originally identified based on its core location in an amplicon on chromosome 20q13.2 in breast cancer cell lines and primary tumors. To understand how ZNF217 overexpression contributes to breast cancer progression, in vitro studies were performed on cultured human mammary epithelial cells (HMEC). Expression of a retrovirally transduced ZNF217 gene in normal finite lifespan and carcinogen-treated extended-life HMEC cultures was found to lead reproducibly to immortalization, a potentially rate-limiting step in the progression of human cancers. HMEC that overcame senescence initially exhibited heterogeneous growth and continued telomere erosion, followed by increasing telomerase activity, stabilization of telomere length, and resistance to TGF beta growth inhibition. Comparative genomic hybridization analysis of ZNF217-immortalized cell lines showed common low level regional DNA-sequence copy number variations on chromosomes 1 and 8 that may be sites of genes that cooperate with ZNF217 in facilitating immortalization. The results obtained support the hypothesis that ZNF217 gene amplification is frequently found in breast cancers because it is involved in enabling breast cells to overcome senescence, thus allowing the cells to continue growing and accumulating other changes necessary for malignant progression. ZNF217 may prove to be a clinically useful marker and a novel therapeutic target.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA398093
Entities
People
- Paul Yaswen
Organizations
- University of California, Berkeley