The Role of Nuclear Receptor Coactivator A1B1 in Growth Factor-Mediated Mammary Tumorigenesis
Annual summary rept. 15 Feb 2006-14 Feb 2007
GEORGETOWN UNIV WASHINGTON DC
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AIB1 Amplified In Breast Cancer 1 is a nuclear receptor coactivator whose gene is amplified in 5-10 of breast cancers and both the mRNA and protein are overexpressed in 30 of breast tumors. In vitro studies show that AIB1 plays a significant role in estrogen and IGF-1-induced cell proliferation. Germline knockout of the AIB1 gene leads to reduced somatic growth, abnormal reproductive function and reduced mammary gland development. Knockout of AIB1 expression also abrogates Rasinduced tumorigenesis. Furthermore, patients with tumors expressing high levels of the growth factor HER2Neu in addition to AIB1 often develop anti-estrogen resistance to tamoxifen therapy. These findings imply that AIB1 plays a fundamental role in the development of hormone-independent breast cancer through growth factor mediated pathways. Nonetheless, the underlying mechanism of AIB1 regulation of growth factor mediated mammary neoplasia is unknown. In this investigation, I will utilize the MMTV-Neu mouse model develop mammary gland tumors in 7-9 months to elucidate the specific role of AIB1 in growth factor-induced mammary tumorigenesis.
- Medicine and Medical Research