Abstract 1130: ING4 tumor suppressor binds to a transcription co-activator, CCAR1, and modulates estrogen-dependent cell growth and gene expression

Abstract

Abstract The tumor suppressor ING4 (Inhibitor of Growth family member 4) has been shown to play a role in diverse cancer-related cellular processes including gene regulation, apoptosis, cell migration, contact inhibition, and angiogenesis. Deletion or reduced expression of ING4 has been shown in various human malignancies including breast cancer, suggesting the tumor suppressive role of ING4. ING4 has been shown to interact with a number of proteins in different cell types, that include p53, NFkB, p300, HBO1-HAT complex, and HPH1. However, the binding partner(s) relevant to the ING4 tumor suppressor function in breast cancer have not been identified. We employed a bacterial two-hybrid screening system using the N-terminal half of the ING4 protein as bait and identified a number of candidate ING4 binding proteins (IBPs). One of the candidate IBPs was CCAR1 (Cell-Cycle and Apoptosis Regulator Protein 1). CCAR1 has recently been characterized as a transcriptional coactivator that is required for estrogen-induced gene expression and cell growth in human breast cancer cells (Kim JH, Yang CK, Heo K, Roeder RG, An W, and Stallcup MR, Mol Cell, 2008). We show the full length ING4 co-immunoprecipitated with endogenous CCAR1 in MCF7 breast cancer cells. In addition, we show that overexpression of ING4 blocked estrogen-dependent cell proliferation of MCF7 cells. These results indicated that ING4 directly binds to CCAR1 and may antagonize the CCAR1 activity required for estrogen-dependent cell growth. We conclude that ING4 may function as a tumor suppressor in breast cancer by modulating estrogen/CCAR1-dependent cell proliferation and gene transcription. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1130.