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Curated Journal Articles on Mesothelioma

CK2¿, over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cell

Journal of Experimental and Clinical Cancer Research 2014 November 25 [Epub ahead of print] [Link]

Zhang S, Yang YL, Wang Y, You B, Dai Y, Chan G, Hsieh D, Kim IJ, Fang L, Au A, Stoppler HJ, Xu Z, Jablons DM, You L.

Abstract

Background

The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation.

Methods

Protein and mRNA levels of CK2¿ and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines. Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay.

Results

In this study, we show that CK2¿ is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2¿ and Gli1 were broadly elevated and correlated (n¿=¿52, r¿=¿0.401, P¿<¿0.05), compared with LP9 (a normal mesothelial cell line). We then investigated their expression at the protein level, and found that all the 7 mesothelioma cell lines tested showed positive staining in CK2¿ and Gli1 immunohistochemistry. Correlation analysis by Pearson test for CK2¿ and Gli1 expression in the 75 mesothelioma tumors and the 7 mesothelioma cell lines showed that the two protein expression was significantly correlated (n¿=¿82, r¿=¿0.554, P¿<¿0.01). Furthermore, we demonstrated that Gli1 expression and transcriptional activity were down-regulated after CK2¿ was silenced in two mesothelioma cell lines (H28 and H2052). CK2¿ siRNA also down-regulated the expression of Hh target genes in these cell lines. Moreover, treatment with a small-molecule CK2¿ inhibitor CX-4945 led to dose-dependent inhibition of Gli1 expression and transcriptional activity. Conversely, forced over-expression of CK2¿ resulted in an increase in Gli1 transcriptional activity in H28 cells.

Conclusion

Thus, we report for the first time that over-expressed CK2¿ positively regulate Hh/Gli1 signaling in human mesothelioma.

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