Wednesday, November 4, 2009
Ballroom A+B (Camino Real Hotel)
Cytochrome P450 2S1 exhibits a unique expression profile among cytochrome P450s. It is one of the few P450 metabolic enzymes that display both selective expression in extrahepatic tissues and constitutive expression throughout development. Elevated CYP2S1 expression is observed in the hyper-proliferative disorders psoriasis and cancer. Increased CYP2S1 expression in colorectal cancer and ovarian cancer correlates with poor prognosis and metastasis, respectively. These data suggest an important role for CYP2S1-mediated metabolism in extrahepatic cells. To determine the role of altered CYP2S1 expression in pulmonary cells, we knocked down CYP2S1 expression, using siRNA, in both human lung alveolar carcinoma cells (A549) and bronchiolar epithelial cells (Beas-2B). CYP2S1 mRNA levels were significantly reduced by approximately 70% in both A549 and Beas-2B cells. CYP2S1 protein was reduced by 50% and 80% in A549 and Beas-2B, respectively. To determine whether alterations in CYP2S1 expression impact the physiology of the cells, we performed cell proliferation assays. In the absence of CYP2S1, A549 and Beas-2B cells exhibit enhanced cellular proliferation. Taken together, these data suggest that CYP2S1-mediated metabolism inhibits cell proliferation. This research was supported by NIH grant #HL60143; NRSA Postdoctoral Fellowship (#F32HL087636) from the National Heart, Lung, and Blood Institute; and the Colgate-Palmolive Postdoctoral Fellowship in In Vitro Toxicology through the Society of Toxicology.