Overexpression of polo-like kinase 1 and its clinical significance in human non-small cell lung cancer.

Abstract

Polo-like kinase 1 is a serine/threonine kinase which plays an essential role in mitosis and malignant transformation. The aim of this study was to investigate the prognostic significance of polo-like kinase 1 expression and determine its possibility as a therapeutic target in non-small cell lung cancer. Semi-quantitative RT-PCR assay was performed to detect polo-like kinase 1 mRNA expression in non-small cell lung cancer cells or tissues. Immunohistochemistry was performed to detect polo-like kinase 1 protein expression in 100 non-small cell lung cancer tissue samples, and the associations of polo-like kinase 1 expression with clinicopathological factors or prognosis of non-small cell lung cancer patients were evaluated. RNA interference was employed to inhibit endogenous polo-like kinase 1 expression and analyzed the effects of polo-like kinase 1 inhibition on the malignant phenotypes of non-small cell lung cancer cells including growth, apoptosis, radio- or chemoresistance. Also, the possible molecular mechanisms were also investigated. The levels of polo-like kinase 1 mRNA expression in non-small cell lung cancer cell lines or tissues were significantly higher than those in normal human bronchial epithelial cell line or corresponding non-tumor tissues. High polo-like kinase 1 expression was significantly correlated with advanced clinical stage, higher tumor classification and lymph node metastasis of non-small cell lung cancer patients (P=0.001, 0.004 and 0.001, respectively). Meanwhile, high polo-like kinase 1 protein expression was also an independent prognostic molecular marker for non-small cell lung cancer patients (hazard ratio: 2.113; 95% confidence interval: 1.326-3.557; P=0.017). Polo-like kinase 1 inhibition could significantly inhibit in vitro and in vivo proliferation, induce cell arrest of G(2)/M phase and apoptosis enhancement in non-small cell lung cancer cells, which might be activation of the p53 pathway and the Cdc25C/cdc2/cyclin B1 feedback loop. Further, inhibition of polo-like kinase 1 could enhance the sensitivity of non-small cell lung cancer cells to taxanes or irradiation. Thus, polo-like kinase 1 might be a prognostic marker and a chemo- or radiotherapeutic target for non-small cell lung cancer.

• Authors: Zhao-Xia Wang, Dong Xue, Zhi-Li Liu, Bin-Bin Lu, Hai-Bo Bian, Xuan Pan, Yong-Mei Yin
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 44 Issue 1 Pg. 200-10 (Jan 2012) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 22064247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• Proto-Oncogene Proteins
• RNA, Messenger
• Protein Serine-Threonine Kinases
• polo-like kinase 1

Topics

• Animals
• Apoptosis (physiology)
• Biomarkers, Tumor (antagonists & inhibitors, biosynthesis, genetics)
• Blotting, Western
• Carcinoma, Non-Small-Cell Lung (enzymology, genetics, pathology, therapy)
• Cell Cycle (physiology)
• Cell Cycle Proteins (antagonists & inhibitors, biosynthesis, genetics)
• Cell Line, Tumor
• Female
• Humans
• Immunohistochemistry
• Lung Neoplasms (enzymology, genetics, pathology, therapy)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Protein Serine-Threonine Kinases (antagonists & inhibitors, biosynthesis, genetics)
• Proto-Oncogene Proteins (antagonists & inhibitors, biosynthesis, genetics)
• RNA Interference
• RNA, Messenger (biosynthesis, genetics)
• Transfection