Decreased PITX1 homeobox gene expression in human lung cancer.

The PITX1 (pituitary homeobox 1) gene has essential roles in human development and has been considered a tumor suppressor in various cancers. However, in lung cancer the role of PITX1 remains to be elucidated. In this study, we analyzed the expression of PITX1 at both mRNA and protein levels in human lung cancer. The reduced PITX1 expression was found in cancer cell lines test compared to normal human bronchial epithelia cells (HEBC) and small airway epithelia cells (SAEC) by Northern blot analysis and RT-PCR as well as Western blot analysis. In primary lung tissues, PITX1 mRNA was found to be downregulated in the majority of tumors compared with normal lung tissues. An association between the lack of PITX1 mRNA expression and higher tumor grade was observed. A tissue microarray containing 135 primary lung carcinomas was analyzed by immunohistochemistry. Eighty-four cases (62%) exhibited no expression of PITX1 and the lower expression of PITX1 was significantly linked to higher tumor stages. Additionally, PITX1 was found to be upregulated in lung cancer cell lines H2228 and H526 after they were exposed to a differentiation modifying agent 5-bromodeoxyuridine (BrdU). Since homeobox genes are known to transcriptionally regulate key cellular processes and associated with differentiation and carcinogenesis, we suggest that PITX1 might be linked to lung cancer development and progression.