Vulnerability of Normal Human Mammary Epithelial Cells to Oncogenic Transformation
Annual rept. 4 Sep 2007-3 Sep 2008
CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
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Breast tumor cells display great diversity in gene and protein expression, and genomic alterations. Distinct cancer subtypes have been categorized, with striking differences in clinical parameters. Our approach to understanding the molecular pathways that lead to the different types of breast cancer in vivo has been to model this process in vitro. However, thus far, almost all in vitro transformed HMEC lines represent a limited subset of in vivo cancer phenotypes. We hypothesized that this could result from restrictive and stressful culture conditions that dont support in vitro growth of the in vivo target cells. Our proposal seeks to generate lines more reflective of breast cancer phenotypes by using our improved, less stressful methods for normal HMEC culture that we now show supports long-term growth of cells with phenotypes of luminal, basal, and progenitor lineages, and to directly examine the effects of stress on vulnerability to oncogenic transformation. In the past year, we have shown that different HMEC populations vary in susceptibility to c-myc mediated transformation, and are currently examining the mechanism for this result. We have also found differences in epigenetic markers among these populations. The generation of diverse transformed HMEC lines with defined genetic alterations may aid the identification of potential therapeutic treatments.
- Anatomy and Physiology
- Medicine and Medical Research