Analysis of cell cycle regulator proteins in non-small cell lung cancer.
ABSTRACT Abnormalities of the proteins involved in cell cycle checkpoints are extremely common among almost all neoplasms. This study aimed to investigate the expression of four components of the cell cycle machinery-p21, p16, p53, and proliferating cell nuclear antigen (PCNA)-in non-small cell lung cancer (NSCLC).
The expression of p21, p16, p53, and PCNA was examined in 68 well characterised NSCLC specimens using immunohistochemistry. The coregulation of these proteins and their influence on survival were analysed using both univariate and multivariate analyses.
By univariate analysis, the expression of all the proteins examined, except for PCNA, was significantly correlated with survival. In multivariate analysis, the only immunohistochemical parameter able to influence overall survival was p16, confirming the hypothesis that the RB-p16 tumour suppressor pathway is inactivated in most lung cancer samples. Finally, the group of patients with NSCLC who were negative for both p21 and p16 had a significantly shorter overall survival.
These results suggest that loss of control of cell cycle checkpoints is a common occurrence in lung cancers, and support the idea that functional cooperation between different cell cycle inhibitor proteins constitutes another level of regulation in cell growth control and tumour suppression.
Full-textDOI: · Available from: Alfonso Baldi, Jun 03, 2015
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ABSTRACT: Mineral dust-induced gene (mdig) can accelerate cell proliferation. The aim of this study is to investigate the mechanism by which mdig regulates cell proliferation. A549 cells were transfected with siRNA specifically targeting mdig. Cell proliferation and cell cycle progression were measured using MTT assay and cell cycle analysis, respectively. Furthermore, real-time reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was performed in A549 cells transfected with mdig siRNA to examine the expression levels of the cell cycle related genes such as p18(INK4c), p19(INK4d), p21(WAF/CIP1), p27(KIP1), p57(KIP2), cyclin D1, and cyclin E. To further explore the effect of mdig on p27(KIP1), the expression levels of total p27(KIP1) and its subtypes pT187-p27(KIP1) and pS10-p27(KIP1) were assessed by Western blotting. In vivo, Western blotting was performed to check the expression levels of mdig and p27(KIP1) in human lung cancer tissues, para-cancerous normal lung tissues, and para-bronchial stumps. Knockdown of mdig induced increases in p27(KIP1), both on mRNA and protein levels. Furthermore, the phosphorylation of p27(KIP1) at its Thr187 site was also inhibited. Importantly, in lung cancer tissues, upregulation of mdig expression accompanies with the downregulation of p27(KIP1) expression and in bronchial stump, vice versa. The data suggest that mdig-mediated inhibition of p27(KIP1) is important for cell proliferation and tumor formation and reveal therapeutic potential of p27(KIP1) for lung cancer.Tumor Biology 04/2015; DOI:10.1007/s13277-015-3397-z · 2.84 Impact Factor
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