Telomerase Independent Telomere Maintenance in Ovarian Cancer: A Molecular Genetic Analysis
Abstract
The goal of this project is to elucidate some of the genetic and biological determinants of ovarian cancer, focusing on an in vitro model for ovarian cancer that we have developed. We found that immortalization and transformation of human ovarian surface epithelial (HOSE) cells can differ in the pathway used for telomere length maintenance, a phenomenon that we have also observed in the clinical disease. We have found that the majority of our HOSE cell cultures use the Alterative Lengthing of Telomeres (ALT) pathway for telomere maintenance, thereby providing an in vitro model to characterize the underlying basis of the ALT pathway in ovarian cancer. In the first year of funding we have completed construction of custom cDNA microarrays and interrogated 50 additional ovarian tumors for telomerase activity. We have also successfully reintroduced telomerase into HOSE cell lines that utilize ALT, characterized these lines and demonstrated that the two pathways, telomerase and ALT, can coexist and used these lines to screen commercial cDNA microarrays for gene expression differences. Validation of gene expression changes is currently underway. Identification of genes important in activating or regulating ALT will provide new targets for the treatment of ovarian cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407268
Entities
People
- Dominique Broccoli
Organizations
- Fox Chase Cancer Center