Structural and Signaling Requirements for C-erbB2 Antiapoptosis in Breast Cancer

The c-erbB2 or HER-2, neu gene encodes a 185-kDa transmembrane glycoprotein pl 85, which belongs to the EGF-r family . The c-erbB2 gene was found to be amplified andor overexpressed in approximately 30 of human breast carcinomas. Our previous studies demonstrated that c-erbB2 overexpression can enhance metastatic potential and confer increased chemoresistance to breast cancer cells, therby leading to poor clinical outcome in breast cancer patients. Our recent studies demonstrated that overexpression of the c-erbB2 gene can protect human breast cancer cells from apoptosis induced by the chemotherapeutic agent Taxol. One of the mechanisms is overexpression of c-erbB2 can upregulate 21 Cip1, which inhibits taxol-mediated p34CdC2 activation, delays cell entrance to O2M phase, and thereby inhibits taxol-induced apoptosis. This new finding provided an explanation on c-erbB2 mediated chemoresistance of breast cancer cells and also explored the importance of p21CPl in G2M phase transition. Since we only use the 435 and its c-erbB2 transfectants in this study, we would like to further confirm this in other c-erbB2 overexpression breast cancer cell lines with different genetic background. Then we will find out whether other p34Cdc2 regulators contribute to taxol