Abstract 4617: Targeting interferon-induced transmembrane protein 1: a novel strategy to treat inflammatory breast cancer

Abstract

Abstract Inflammatory breast cancer (IBC) is a very rare and aggressive form of breast cancer that accounts for about 1 to 5% of all breast cancers diagnosed in the United States. IBC is characterized by absence of a discrete mass, coupled with very rapid progression and dermal lymphatic invasion, which makes it the most lethal of the breast cancers. IBC is currently treated by a multimodal approach involving systemic chemotherapy, surgery, followed by radiation therapy; however, this strategy has yielded a 5-year survival outcome of only 20 to 30%. There is an urgent need to better understand the molecular mechanism that contributes to the development of IBC and to use that knowledge to identify novel targets that can be manipulated to enhance treatment options for IBC patients. In the present study, we have examined the role of human interferon-inducible transmembrane protein 1 (IFITM1) in the proliferation and invasion of inflammatory breast cancer. IFITM1 is a member of the interferon-inducible transmembrane protein family, which is involved in many cellular functions, including the transduction of antiproliferative and homotypic adhesion signals in lymphocytes, inhibition of viral replication, and promotion of cell invasion. At present, however, very little is known about the function of IFITM1 in inflammatory breast cancer. Our in vitro studies were performed in human inflammatory breast cancer cell lines; SUM149, SUM190, MDA-IBC-3, and non-inflammatory MCF-7 breast cancer cells. We found that IFITM1 mRNA and protein levels were constitutively overexpressed in SUM149 and MDA-IBC-3 cell lines but not expressed in non-inflammatory MCF-7 cells. Functional analysis of IFITM1 by silencing of its expression with small-interfering RNA showed that the loss of IFITM1 significantly inhibited the proliferation and invasiveness of SUM149 and MDA-IBC-3 cells and it completely blocked the ability of these cells to form colonies in soft agar assays. Interestingly, we found that interferon (IFN-α) significantly induced IFITM1 expression in all three of the IBC cell lines; however, IFN-α treatment inhibited the proliferation and invasiveness of the IBC cells. Our data also showed that several other interferon-regulated genes, including STAT1, PLSCR1, and STAT6 were elevated in inflammatory SUM149, MDA-IBC-3, and SUM190 cells but not in non-inflammatory MCF-7 cells. Overall, these results demonstrate that IFITM1 plays an important role in the proliferation and invasiveness of IBC cells and they suggest that targeting IFITM1 might be a novel strategy to treat inflammatory breast cancer. Citation Format: Joshua W. Ogony, Joan Lewis-Wambi. Targeting interferon-induced transmembrane protein 1: a novel strategy to treat inflammatory breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4617. doi:10.1158/1538-7445.AM2014-4617