Cooperative Interactions During Human Mammary Epithelial Cell Immortalization
Abstract
Our laboratory has pioneered the development and use of cultured human mammary epithelial cells (HMEC) to gain information on the defects in growth control processes that allow finite lifespan HMEC to overcome all senescence barriers, reactivate telomerase, and gain immortal potential. We hypothesize that, due to the stringency of telomerase repression in humans, attaining these defects may be a key rate-limiting step in human carcinogenesis. The goal of this project has been to define the minimum number of genetic and epigenetic changes that permit telomerase reactivation and immortal transformation of finite lifespan HMEC, in a manner that models changes observed in breast cancers in vivo. During the past year, we were able to obtain immortalized HMEC using a combination of two oncogenes (c-myc and ZNF2l7) with pathological relevance to human breast cancer. Comparative genomic hybridization (CGH) analyses of two immortal populations obtained using c-myc and ZNF2l7 did not show any detectable additional changes in gene copy numbers, suggesting that along with unknown epigenetic changes, over-expression of these 2 genes together might be sufficient for immortalization. Better understanding of the underlying molecular changes involved in telomerase reactivation may provide novel prevention strategies and/or targets for therapeutic intervention in breast cancer pathogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA419150
Entities
People
- Paul Yaswen
Organizations
- University of California, Berkeley