Mainstream and Sidestream Cigarette Smoking Induces Overexpression of TSPO and Cell Proliferation in Human Breast Cancer Cell Lines

Several epidemiological studies have linked cigarette smoking to breast cancer, particularly in young women. However, there is no scientific validity of this link. TSPO, formerly known as p eripheral benzodiazepine receptor (PBR) is highly expressed in aggressive human breast cancer cell lines and breast tumor tissues. The present study investigates whether exposure of mainstream (MS) as well as sidestream (SS) cigarette induces TSPO‐mediated cell proliferation in a variety of human breast cancer epithelial cell lines and if so what is the mechanistic link. Human breast cancer cell lines (MCF10, MCF 12A and MCF 12F) were grown in DMEM/F‐12 and exposed to either MS or SS smoke generated from 1R3F cigarettes in a THRI MS‐SS smoke exposure machine using the modified version of CULTEX cell culture smoke exposure system. A sham control (SH) group was also used where cells were exposed to the same environmental condition without smoke exposure. Induction of cell proliferation was observed at low doses whereas cellular apoptosis was observed at high doses in all cell lines regardless of MS and SS exposure. A combination of immunohistochemical, Western blot and receptor binding studies revealed an overexpression of TSPO in all cell lines by both MS and SS smoke. Furthermore, both MS and SS smoke caused a higher levels of TSPO in nuclei associated with an increase in nuclear cholesterol transport. These TSPO‐mediated effects of smoke exposure on breast cancer cell lines were counteracted by PK11195, a TSPO antagonist, suggesting a therapeutic potential of PK11195 in controlling breast cancer development. ( Supported by FAMRI Clinical Innovator Award # 062415 ).