Abstract 4201: Role of adenomatous poliposis coli (APC) in cigarette smoke condensate-induced accumulation of apurinic/apyrimidinic lesions and enhanced transformation of normal breast epithelial cells

Abstract

Abstract Active and passive smoking are major risk factors for cancer and have been implicated in the etiology of breast cancer. The mechanisms through which smoking promotes breast cancer are poorly understood. Our previous studies have shown that cigarette smoke condensate (CSC), a surrogate for cigarette smoke, induces transformation of normal human breast epithelial (MCF10A) cells in culture. We have described the involvement of a multifunctional protein, adenomatous polyposis coli (APC), in the CSC-induced transformation of MCF10A cells through the interaction with DNA polymerase β and 5’-flap endonuclease 1 (Fen1), and thus, the blockade of the BER pathway. In the present study, we have examined the underlying mechanisms involved in CSC and Benzo[α]pyrene (B[α]P)-induced transformation of MCF10A cells in which APC was overexpressed or knocked down. Our results suggest a positive correlation between the increased levels of APC expression with the decreased BER activity and concomitant accumulation of apurinic/apyrimidinic (AP)-site lesions. If not repaired on time, the cytotoxic and mutagenic AP-site lesions ultimately lead to enhanced transformation of MCF10A cells. These studies suggest a possible mechanism by which active and/or passive cigarette smoking might be linked with breast carcinogenesis. This work was supported by Flight attendant Medical Research Institute, Miami, FL to SN. 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 4201. doi:10.1158/1538-7445.AM2011-4201