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Published on: November 5, 2019
Mutations of the Cx43 Gene in Non-Small Cell Lung Cancer: Association with Aberrant Localization of Cx43 Protein
Jung-Chien Chen1,2,3, Kun-Tu Yeh4,5, Yueh-Min Lin6,7
1Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Abstract:
Background and Objectives: The Connexin43 (Cx43) gene is a suspected tumor suppressor gene, as re-expressed wild-type Cx43 genes reduce the malignancy potential of tumor cells. However, the role of Cx43 gene expression in human lung tumorigenesis remains unclear. Materials and Methods: 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, Cx43 genes with or without mutations were transfected to CL-3 human lung cancer cells to confirm the function of these mutant forms of the Cx43 gene. Results: 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 Cx43 gene were also found in patients with aberrant Cx43 localization, and transfection of these mutant genes into lung cancer cells enhanced their proliferation. Conclusions: To our knowledge, this is the first study to demonstrate Cx43 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.
Insights
Connexin43 (Cx43) gene mutations were identified in human lung cancer, suggesting Cx43 acts as a tumor suppressor. Aberrant Cx43 protein localization correlated with enhanced lung cancer cell proliferation.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Connexin43 (Cx43) is implicated as a tumor suppressor gene, with re-expression of wild-type Cx43 reducing tumor cell malignancy.
- The specific role of Cx43 gene expression in human lung tumorigenesis requires further elucidation.
Purpose of the Study:
- To investigate the presence and functional significance of Cx43 gene mutations in human lung cancer.
- To determine the association between Cx43 protein expression, localization, and non-small cell lung cancer (NSCLC) progression.
Main Methods:
- Immunohistochemistry and direct DNA sequencing were employed to analyze Cx43 protein expression and gene mutations in 165 primary lung cancer tissues.
- Functional analysis involved transfecting CL-3 human lung cancer cells with wild-type and mutant Cx43 genes.
Main Results:
- Aberrant nuclear and cytoplasmic localization of Cx43 protein was observed in 14 out of 165 NSCLC patients.
- Cx43 gene mutations were detected in patients with aberrant Cx43 localization, and these mutations enhanced lung cancer cell proliferation upon transfection.
Conclusions:
- This study provides the first evidence of Cx43 gene mutations in human lung neoplasms, supporting its role as a potential tumor suppressor in a subset of lung cancer patients.
- Aberrant Cx43 protein expression localization is linked to tumor progression in lung cancer.
