Wnt5a is associated with cigarette smoke-related lung carcinogenesis via protein kinase C

• Published in: PloS one 2013-01, Vol.8 (1), p.e53012
• Main Authors: Whang, Young Mi, Jo, Ukhyun, Sung, Jae Sook, Ju, Hyun Jung, Kim, Hyun Kyung, Park, Kyong Hwa, Lee, Jong Won, Koh, In Song, Kim, Yeul Hong
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; AKT protein; Apoptosis; Apoptosis - drug effects; B cells; Blockage; Bronchi - cytology; Cancer; Carcinogenesis; Carcinogens; Cell growth; Cell survival; Cell Survival - drug effects; Cell Transformation, Neoplastic - chemically induced; Cigarette smoke; Cigarettes; Colonies; Enzyme Activation - drug effects; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Exposure; Forming; Gene Expression Regulation, Neoplastic - drug effects; Hematology; Humans; Kinases; Lung cancer; Lung diseases; Lung Neoplasms - chemically induced; Lung Neoplasms - enzymology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medicine; mRNA; Non-small cell lung cancer; Non-small cell lung carcinoma; Oncology; Protein kinase C; Protein Kinase C - metabolism; Protein kinases; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Ribose; RNA; Science; Signal Transduction - drug effects; Smoke; Smoke - adverse effects; Smokers; Smoking; Survival; Tissues; Tobacco; Tobacco Products - adverse effects; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt-5a Protein
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053012

Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate (CSC). Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis.