ALTERED CJUN EXPRESSION - AN EARLY EVENT IN HUMAN LUNG CARCINOGENESIS

Although the c-jun oncogene is an integral part of the AP-1 transcript ional complex implicated in the process of tumor promotion, its role i n the pathogenesis of human tumors is unknown. We analyzed the express ion and function of cJun in 110 non-small cell lung cancer (NSCLC) pri mary and metastatic tumors, histologically atypical areas from the sur rounding lung, and 10 NSCLC cell lines to examine the role Of cJun in lung carcinogenesis, cJun was expressed in primary and metastatic lung tumors in 31% of cases, with no association with survival. Whereas no rmal conducting airway and alveolar epithelia in general did not expre ss cjun by immunohistochemistry, histologically atypical areas were fr equently positive for cJun, regardless of the status of the correspond ing tumor. Multiple members of the jun and fos gene families were freq uently expressed at the mRNA level in vitro, with detectable functiona l activity (as defined by AP-1-specific DNA binding and/or transactiva tion of an AP-1-driven reporter construct) present in all 10 NSCLC cel l lines examined. Although tumor-promoting phorbol esters had little e ffect on c-jun expression, serum stimulation generally resulted in sig nificant c-jun induction in NSCLC cell lines. These data show that cJu n expression is altered early during human lung carcinogenesis and tha t dun may function as a mediator of growth factor signals in NSCLC.