Abstract A040: Id-1 increases mammary basal stem cell activity and tumorigenesis by activating the Wnt/c-Myc pathway

Abstract

Abstract Inhibitor of differentiation/DNA binding (Id)-1 is a crucial regulator of mammary development and breast cancer progression. Here, we demonstrate that Id-1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities. MaSC expansion and increased self-renewal and in vivo regenerative capacity of MaSCs were observed in the mammary glands of MMTV-Id-1 transgenic mice. Id-1 maintains the MaSC-enriched basal cells, but not the luminal cell lineage, in the mammary glands. Furthermore, Id-1 induces ductal hyperplasia and mammary tumors with high expression of basal markers in MMTV-Id-1 transgenic mice. It also increases breast cancer stem cell populations and activity in human breast cancer lines. In experiments with mouse primary mammary epithelial cells and human cancer cells, the effects of Id-1 on normal and cancer stem cell activity were shown to be mediated by the Wnt/c-Myc pathway. Collectively, these findings indicate that Id-1 regulates mammary basal stem cells by activating the Wnt/c-Myc pathway, thereby contributing to basal marker-positive breast tumor development. Citation Format: Dong-Hui Shin, Jeong-Yeon Lee, Ki-Seok Jang, Kyueng-Whan Min, Si-Hyong Jang, Seung Hyun Oh, Gu Kong. Id-1 increases mammary basal stem cell activity and tumorigenesis by activating the Wnt/c-Myc pathway. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A040.