Elucidating the Role of Cks Proteins in Breast Cancer by Combining the Disciplines of Molecular Biology, Pathology, and Biophysics; Annual rept. 1 Mar 2007-28 Feb 2008

摘要

Breast cancer often occurs when the proteins that regulate normal epithelial cell division become dysregulated. This proposal examines the role of the cell cycle regulatory proteins human cyclin-dependent kinase subunits (Cks1 and Cks2) in human breast cancer. The overexpression of Cks genes in breast tumor tissue and the role of Skp2 in tumorigenesis suggests that Cks and Skp2 levels must be strictly regulated for proper cell cycling. We hypothesize that aberrant Cks protein expression and function contributes to breast carcinogenesis at least in part by its ability to interact with Skp2. In year one of this project we have determined the levels of Cks mRNA and protein in (i) breast cancer cell lines and (ii) normal versus tumor breast tissue. We have also developed breast cancer cell lines that overexpress cksl cks2 or skp2 and cells that co-overexpress cks2 and skp2. In the coming year we will focus on characterizing the breast cancer cell lines developed that stably overexpress the aforementioned cell cycle proteins using both in vitro and in vivo techniques.