Mutations of the Cx43 Gene in Non-Small Cell Lung Cancer: Association with Aberrant Localization of Cx43 Protein Expression and Tumor Progression

<i>Background and Objectives</i>: The Connexin43 (<i>Cx43</i>) gene is a suspected tumor suppressor gene, as re-expressed wild-type <i>Cx43</i> genes reduce the malignancy potential of tumor cells. However, the role of <i>Cx43</i> gene expression in human lung tumorigenesis remains unclear. <i>Materials and Methods:</i> Tumor tissues from 165 primary lung cancer patients were collected to study Cx43 protein expression and gene mutations using immunohistochemistry and direct DNA sequencing. In addition, <i>Cx43</i> genes with or without mutations were transfected to CL-3 human lung cancer cells to confirm the function of these mutant forms of the <i>Cx43</i> gene. <i>Results:</i> Aberrant localization of Cx43 protein in the nucleus and cytoplasm of tumor cells was detected in 14 out of 165 non-small cell lung cancer (NSCLC) patients. Mutations in the <i>Cx43</i> gene were also found in patients with aberrant Cx43 localization, and transfection of these mutant genes into lung cancer cells enhanced their proliferation. <i>Conclusions:</i> To our knowledge, this is the first study to demonstrate <i>Cx43</i> gene mutations in human lung neoplasm, supporting the hypothesis that Cx43 may function as a tumor suppressor in some lung cancer patients. Additionally, the findings suggest an association between aberrant localization of Cx43 protein expression and tumor progression.