Breast Cancer: Current Research
Open Access

Abstract

Gene amplification in the 17q chromosomal region is observed frequently in breast cancers. An integrative bioinformatics analysis nominated MAP3K3 gene, located in 17q23, as a potential therapeutic target in breast cancer. This gene encodes the mitogenactivated protein kinase kinase kinase 3 (MEKK3), but has not yet been associated with cancer-causal genetic aberrations. We found that MAP3K3 was amplified in approximately 8-20% of breast carcinomas, and that its over-expression was an independent prognostic marker for poor outcome with respect to relapse-free and overall survival, especially among the estrogen receptor-positive breast cancer patients. shRNA- mediated knockdown of MAP3K3 expression significantly inhibited cell proliferation and colony formation of MAP3K3-amplified breast cancer cell lines MCF7 and MDA-MB361, and promoted breast cancer cell apoptosis induced by TNFα, TRAIL, or a doxorubicin. In addition, ectopic expression of MAP3K3, in collaboration with Ras, induced colony formation in both primary mouse embryonic fibroblasts and immortalized mammary epithelial cells (MCF-10A). Together, these results suggest that MAP3K3 is a potential biomarker indicating poor prognosis, contributes to resistance to therapy, and is an oncogene in breast carcinogenesis. Therefore, therapeutic targeting of MAP3K3 may be attractive in breast cancer patients with MAP3K3-amplified breast cancer.

Biography

Amy Hong Zhang is currently an Associate Professor in the Department of Pathology and Translational Molecular Pathology in University of Texas-MD Anderson Cancer Center in Houston, TX, specializing on breast cancer pathology. She is an American Board certified practicing Pathologist since 2003. She has expertise in diagnosing breast cancers and the interpretation of the biomarkers relevant to breast cancers for patient care. She is also actively supervising research scientists and trainees on translational and laboratory research, focusing on the characterization of tumor markers significant for breast tumorigenesis and the development of small molecule inhibitors and potential novel molecular targets for breast cancer treatments in a different way of focusing.

Email: HZhang9@mdanderson.org