Abstract 3021: FoxP1 increases nucleotide excision repair capacity through activating xeroderma pigmentosum group C in human breast cancer

Abstract

Abstract Breast cancer is the most common cancer in the women. Recent study revealed that nucleotide excision repair (NER) deficiency might play an important role in the cause of sporadic breast cancer, showing significant reduction of five NER gene products including xeroderma pigmentosum group C (XPC) in human breast cancer tissue. Thus, XPC inactivation might be related to occurrence and progression of breast cancer. FoxP1 is a member of the forkhead O family of transcription factors which have a broad range of functions. FoxP1 is considered as a putative tumor suppressor in breast cancer because of its ability to cause apoptosis. The relationship between FoxP1 and XPC has been yet to be known in breast cancer. In our data, Western blot analysis of 8 human primary tumors showed that the high expression of FoxP1 was correlated with the high level of XPC. In three established mammary epithelial cell lines (MCF-7, MDA-MB-231, 4T1), FoxP1 expression in MCF-7 was higher than in MDA-MB-231 and 4T1. Similar to the result of primary tumors, the expression of XPC was also high in MCF-7 and low in MDA-MB-231 and 4T1. Next, we found that the level of XPC decreased with the knockdown of FoxP1 compared to control in MCF-7. On the other hand, the ectopic expression of FoxP1 in MDA-MB-231 and 4T1 elevated XPC expression for protein level. In real time RT-PCR, the level of XPC mRNA was the same as in Western blot analysis. We tested whether NER activity is dependent on FoxP1. In vitro NER activity increased by overexpression of FoxP1 in MB-231. Sh-FoxP1 transfected MCF-7 cell shows reduced in vitro NER activity. In addition, immunostaining assay showed that XPC expression was much accumulated in the nucleus of MDA-MB-231 with overexpression of FoxP1 than in control.Taken together, these data suggested FoxP1 could up-regulate NER activity by activating XPC in breast cancer. However, the way how FoxP1 can regulate XPC remained to be cleared. To clarify the mechanism, we are performing biological interaction between FoxP1 and XPC in both breast cancer cell lines and human primary breast tumors. Citation Format: Haesung Kim, Lee-Su Kim, Jae-yong Lee, Jeong-Hyeon Kim, Jeong-Min Lee, Chea-Ha Kim. FoxP1 increases nucleotide excision repair capacity through activating xeroderma pigmentosum group C in human breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3021. doi:10.1158/1538-7445.AM2015-3021