Rarres1 Is A Tumor Suppressor In Triple-Negative Breast Cancer Cell Lines

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Increasing evidence suggests that retinoic acid (RA) signaling is of great importance in the progression and metastasis of different cancer types. We have previously reported that MDA-MB-231 and MDA-MB-468 triple-negative breast cancer cell lines display different responses to increased retinoic acid: retinoic acid increases MDA-MB-231 xenograft growth and decreases growth MDA-MB-468 xenografts. To investigate what may be responsible for these opposite responses to RA, we have investigated the role of retinoic acid receptor responder protein 1 (RARRES1). RARRES1 is an RA-inducible gene which has not yet been fully characterized. Despite its unknown function, many independent studies have reported the tumor suppressive function of RARRES1 in multiple cancer types. Interestingly, our previous data indicates that high levels of RARRES1 in clinical breast cancer samples is correlated with poorer outcomes for patients. In particular, high expression of RARRES1 is associated with triple-negative breast cancers as well as with more aggressive cancers (by Ki67 positivity, as well as nuclear, mitotic, and overall grade). Thus, to determine the role of RARRES1 in breast cancers, we have performed in vitro cell proliferation and in vivo xenograft assays. We report that knockdown of RARRES1 in MDA-MB-231 and MDA-MB-468 cells leads to increased cell proliferation in vitro and in in vivo xenografts. RARRES1 is proposed to regulate a number of genes, including the hypothesized tumor suppressors discs large homolog 2 and protein phosphatase 2A, the proto-oncogene valosin-containing protein (p97), and ankyrin repeat domain-containing protein 26 which is of unknown function. We are investigating the regulation of these genes by RARRES1 in MDA-MB-231 and MDA-MB-468 triple-negative cell lines. We expect that the RARRES1 tumor suppressor is one of many genes induced by RA which form a complex signaling pathway regulating the response of cells to RA. We conclude that RARRES1 is a tumor suppressor in MDA-MB-231 and MDA-MB-468 triple-negative breast cancer cell lines; however, we continue to investigate the discrepancy between this finding and our previous clinical data. Citation Format: Krysta M. Coyle, Ahmad Vaghar-Kashani, Florence Wong, Cheryl Dean, Carman Giacomantonio, Paola Marcato. RARRES1 is a tumor suppressor in triple-negative breast cancer cell lines. [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 578. doi:10.1158/1538-7445.AM2014-578