Abstract 4018: The role of FLI1 in breast cancer development and progression

Abstract

Abstract Breast cancer is the second most common cancer-related death among women in the US. The majority of the breast cancer-related deaths are due to tumor progression. A multitude of changes in gene expression are required for the cancer cell to acquire the ability to invade and migrate. The transcriptional activation or repression of these cancer-associated genes is not clearly understood, however many ETS family members have been considered good candidates. Friend leukemia virus integration 1 (FLI1) is an ETS protein that is aberrantly expressed in retrovirus-induced hematological tumors, and is found to be rearranged in Ewing's sarcoma and related primitive neuroectodermal tumors characterized by a t(11;22)(q24;q12) translocation. Limited attention has been directed towards elucidating the potential role of FLI1 in epithelial-derived cancers, including breast cancer. Our preliminary immunohistochemical analyses show that FLI1 protein is decreased in human invasive breast tumors compared to normal breast tissue. A decrease of FLI1 mRNA and protein was also demonstrated in breast cell cancer cell lines through Real Time RT-PCR and western blot, respectively. We used adenovirus to examine the effects of FLI1 expression in two invasive breast cancer cell lines (MDA-MB-231 and MDA-MB-157). Re-expression of FLI1 in both MDA-MB-231 and MDA-MB-157 inhibited cell growth, mainly due to a decrease in cellular proliferation. FLI1 expression also inhibited the motility and invasiveness of breast cancer cell lines, determined by the use of Transwell inserts coated with fibronectin or Matrigel, respectively. We hypothesize that the loss of FLI1 is a critical step for breast cancer progression. Loss-of-function studies using shRNA are being performed to complement the above gain-of-function studies. Future studies will investigate potential downstream targets of FLI1. Inhibiting the reduction of FLI1 or regulating its downstream targets may be to be unique targets of breast cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4018. doi:10.1158/1538-7445.AM2011-4018