The effect of xeroderma pigmentosum group C (XPC) on squamous cell lung cancer

Lung cancer remains the leading cause of cancer-related deaths. Squamous cell lung cancer (SCC) is strongly linked to cigarette smoking and develops from pulmonary epithelial cells. DNA repair is critical to prevent mutations which lead to cancer. These studies aim to determine the mechanistic link between decreased DNA repair and development of lung SCC. XPC is a DNA repair protein involved in the global-genomic nucleotide excision repair pathway, and decreased XPC has been observed in human lung cancers and with chronic cigarette smoking in mice. Our laboratory found that mice deficient in XPC were prone to develop SCC following exposure to the carcinogen NTCU. We hypothesized that XPC-deficient mice treated with NTCU would develop pre-malignant changes in pulmonary epithelial cells earlier than NTCU-treated XPC proficient mice. Mice 8-, 10-, 12-, and 16-weeks after NTCU treatment were analyzed by immunofluorescence microscopy for percent epithelial cells expressing CK5/6+, a marker of malignant epithelial cell transformation. Lung SCCs were CK5/6+, and increased CK5/6 percent-positive in large compared to small airways at all time points, with CK 5/6 staining increasing over time. Ongoing analysis will determine whether XPC expression is associated with differences in CK 5/6 expression at different time points by airway size.