['Monoclonal antibodies, such as herceptin and trastuzumab, against the epidermal growth factor receptor ErbB2 (also known as HER2/neu) are an effective therapy for breast cancer patients with overexpression of ErbB2. Herceptin, in combination with standard chemotherapy, such as taxol or etoposide, gives a synergistically apoptotic response in breast tumors.', 'The mechanism underlying this synergy between chemotherapy and herceptin treatment is not well understood. Herein, we have determined that addition of herceptin, sensitized breast cancer cell lines MDA-MB-231 and MCF-7 to etoposide- or taxol-induced apoptosis.', 'This treatment resulted in reduced expression of ErbB2 and the antiapoptotic Bcl-2 family member Mcl-1 in MDA-MB-231 cells. Using antisense oligonucleotides against Mcl-1, MDA-MB-231 cells were rendered sensitive to etoposide-induced apoptosis similar to herceptin, but combined treatment of antisense against Mcl-1 and herceptin failed to give a significant increase in apoptosis. In 29 human breast tumors immunostained for ErbB2 and Mcl-1, we found that when ErbB2 was overexpressed, there was a corresponding increase in Mcl-1 expression.'] Does herceptin sensitize ErbB2-overexpressing cells to apoptosis by reducing antiapoptotic Mcl-1 expression?