Role of Nuclear Receptor Coactivator A1B1 in Growth Factor-Mediated Mammary Tumorigenesis; Annual summary

摘要

AIBI (Amplified In Breast Cancer I) 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 AIBI plays a significant role in estrogen and IGF-1-induced cell proliferation. Germline knockout of the AIBI gene leads to reduced somatic growth abnormal reproductive function and reduced mammary gland development. Knockout of AIBI expression also abrogates Ras-induced tumorigenesis. Furthermore patients with tumors expressing high levels of the growth factor HER2/Neu in addition to AIBI often develop anti-estrogen resistance to tamoxifen therapy. These findings imply that AIBI plays a fundamental role in the development of hormone-independent breast cancer through growth factor mediated pathways. Nonetheless the underlying mechanism of AIBI regulation of growth factor mediated mammary neoplasia is unknown. In this invesbgation I will utilize the MMTV-Neu mouse model (develop mammary gland tumors in 7-9 months) to elucidate the specific role of AIBI in growth factor-induced mammary tumorigenesis.