| Lung cancer is a leading cause of death worldwide. Over the past decade, much has been learned about the molecular alterations associated with lung cancer, however, the precise mechanisms underlying lung carcinogenesis remain unresolved.In this study, fifty-one functionally unknown genes, which were potentially related to lung cancer, were cloned and further screened with functional and phenotypic methods. We found a novel gene which could both activate NF-kappaB reporter activity and induce NIH/3T3 cell transformation with the increased foci formation. We named it OLC1 (overexpressed in lung cancer). OLC1 was transfected into NIH/3T3 cells, and the oncogenic function was evaluated by both in vitro and in vivo experiments. Small interfering RNAs (siRNA) directly against OLC1 were used to determine the role of OLC1 in the tumor cell growth. Immunohistochemical analysis was used to determine the OLC1 expression level in a tissue microarray containing formalin-fixed, paraffin-embedded tissue specimens of lung cancer.We showed that NIH/3T3 cells with enforced OLC1 overexpression grew at an accelerated rate and gained increased anchorage-independent growth capability. Nude mouse xenograft studies showed that NIH/3T3 cells overexpressing OLC1, but neither parental nor empty vector control-transfected cells produced fibrosarcomas. Silencing expression of OLC1 using siRNA resulted in inhibition of growth and increased apoptosis in both H520 and H1299 lung cancer cell lines. Using immunohistochemical staining, overexpression of OLC1 was detected in the most frequent types of lung cancers, as well as pulmonary premalignant lesions. Furthermore, overexpression of OLC1 led to constitutive activation of NF-kappaB pathway in cancer cells.Taken together, our studies provide strong evidence that OLC1 plays an important role in the tumorigenesis of human lung. We also indicate the importance of OLC1 as a potential early diagnostic and therapeutic target for human cancers.
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