Functional Analysis of a Novel Transcription Factor that is Amplified and Overexpressed in Breast Cancers
Abstract
The candidate oncogene ZNF2l7, predicted to encode alternately spliced Kruppel-like transcription factors, was originally identified based on its core location in an amplicon on chromosome 2Oq13.2 in breast cancer cell lines and primary tumors, and its recurrent pattern of expression in tumors. To understand how ZNF2l7 overexpression contributes to breast cancer progression, in vitro studies are being performed to determine how ZNF2l7 alters the phenotype of human mammary epithelial cells (HMEC). Initially, we investigated the functional consequences of ZNF2l7 overexpression by transducing the gene into finite lifespan HMEC. In five independent experiments, ZNF2l7-transduced cultures maintained growth beyond the point where control cells senesced. HMEC that overcame senescence initially exhibited heterogeneous growth and continued telomere erosion, followed by increasing telomerase activity, stabilization of telomere length, and resistance to TGFbeta growth inhibition. This pattern is similar to that observed in rare HMEC lines immortalized following exposure to a chemical carcinogen, where telomerase reactivation and attainment of good uniform growth occurred in an incremental, apparently epigenetic manner, a process we have termed "conversion," as a consequence of overcoming senescence. Aberrant expression of ZNF217 may be selected for during breast cancer progression because it allows breast cells to overcome senescence and attain immortality.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA396851
Entities
People
- Paul Yaswen
Organizations
- University of California, Berkeley