Abstract
BackgroundThe aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 (CDK4) in lung cancer and its correlation with clinicopathologic features. Furthermore, the involvement of CDK4-mediated cell cycle progression and its molecular basis were investigated in the pathogenesis of lung cancer.MethodsUsing immunohistochemistry analysis, we analyzed CDK4 protein expression in 89 clinicopathologically characterized lung cancer patients (59 males and 30 females) with ages ranging from 36 to 78 years and compared them to 23 normal lung tissues. Cases with cytoplasmic and nuclear CDK4 immunostaining score values greater than or equal to 7 were regarded as high expression while scores less than 7 were considered low expression. The correlation between the expression level of CDK4 and clinical features was analyzed. Furthermore, we used lentiviral-mediated shRNA to suppress the expression of CDK4 and investigate its function and molecular mechanism for mediating cell cycle progression.ResultsThe expression level of CDK4 protein was significantly increased in lung cancer tissues compared to normal tissues (P < 0.001). In addition, high levels of CDK4 protein were positively correlated with the status of pathology classification (P = 0.047), lymph node metastasis (P = 0.007), and clinical stage (P = 0.004) of lung cancer patients. Patients with higher CDK4 expression had a markedly shorter overall survival time than patients with low CDK4 expression. Multivariate analysis suggested the level of CDK4 expression was an independent prognostic indicator (P < 0.001) for the survival of patients with lung cancer. Use of lentiviral-mediated shRNA to inhibit the expression of CDK4 in lung cancer cell line A549 not only inhibited cell cycle progression, but also dramatically suppressed cell proliferation, colony formation, and migration. Furthermore, suppressing CDK4 expression also significantly elevated the expression of cell cycle regulator p21ConclusionOverexpressed CDK4 is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression of p21 in lung cancer
Highlights
The aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 (CDK4) in lung cancer and its correlation with clinicopathologic features
The expression level of CDK4 protein was significantly increased in lung cancer tissues compared to normal tissues (P < 0.001)
Use of lentiviral-mediated shRNA to inhibit the expression of CDK4 in lung cancer cell line A549 inhibited cell cycle progression, and dramatically suppressed cell proliferation, colony formation, and migration
Summary
The aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 (CDK4) in lung cancer and its correlation with clinicopathologic features. CDK4 is part of the cyclin-dependent kinase family. The protein encoded by this gene is a member of the Ser/Thr protein kinase family and is highly similar to the gene products of S. cerevisiae cdc and S. pombe cdc. The protein encoded by this gene is a member of the Ser/Thr protein kinase family and is highly similar to the gene products of S. cerevisiae cdc and S. pombe cdc2 It is a catalytic subunit of the protein kinase complex important for G1 cell cycle progression. Overexpression of CDK4 has been showed in many tumor types, including oral squamous cell carcinoma [3], pancreatic endocrine tumors [4], lung cancer [5,6], and nasopharyngeal carcinoma [7], suggesting that CDK4 is a key factor in promoting the initiation and development of tumors
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