The Improvement of Human Cyr61 in Heregulin Induction of Breast Tumor Progression
Annual summary rept. 1 Aug 2001-31 Jul 2002
CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
Pagination or Media Count:
This fellowship initially concerned the role of the cytokine, heregulin, in the regulation of hormone receptor status in breast cancer. The mechanism by which breast cancer progresses from an ER to an ER- is of considerable clinical importance because some estrogen receptor-positive ER breast tumors may progress to ER-negative andor to deadly metastatic diseases. The justification for changing the project so late in the term is that Dr. Ruth Lupu, the mentor on the original award, left the LBNL shortly after I moved to the US to join the lab. Personal circumstances prevailed in my decision to change my mentor to Dr. Mary Helen Barcellos-Hoff and stay at LBNL. Recent studies in Dr. Barcellos-Hoff lab showed that depletion of transforming growth factor-beta TGF-Beta, in the TgfBeta1 null mouse mammary gland leads to increased frequency of proliferating ER cells, and indeed increased numbers of ER cells as detected by immunofluorescence. Therefore, we proposed to change the focus of the award from heregulin to TGF-Beta1-, which is also known to regulate heregulin. In the last 3 months, I have shown by Western blot analysis of mammary gland extracts of wild type and TgfBeta1 heterozygotes mice that the ER level is higher in heterozygotes than wild type, consistent with the immunofluoresence data. As a continuation of this work on ER regulation, I will investigate how TGF-Beta1 suppresses ER using primary mouse mammary cell culture.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research