Cooperative Interactions During Human Mammary Epithelial Cell Immortalization
Abstract
Our laboratories have developed and utilized 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 rate-limiting in human carcinogenesis. Our goal is 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. Thus far, we have been able to obtain immortalized HMEC using a combination of two oncogenes (c-myc and ZNF217) with pathological relevance to human breast cancer. Although CGH analyses of some of these immortal lines did not show any detectable large-scale changes in gene copy numbers, these lines have all undergone clonal selection, suggesting that unknown stochastic changes, in addition to over-expression of c-myc and ZNF217, might be necessary for immortalization. We are currently working to identify these stochastic changes. 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, 2004
- Accession Number
- ADA432807
Entities
People
- Paul Yaswen
Organizations
- University of California, Berkeley