TY - JOUR T1 - Functional polymorphism of the CK2alpha intronless gene plays oncogenic roles in lung cancer. JF - PLoS One Y1 - 2010 A1 - Hung, Ming-Szu A1 - Lin, Yu-Ching A1 - Jiang-Hua Mao A1 - Kim, Il-Jin A1 - Xu, Zhidong A1 - Yang, Cheng-Ta A1 - Jablons, David M A1 - You, Liang KW - Animals KW - Blotting, Western KW - Casein Kinase II KW - Cell Line KW - Cell Line, Tumor KW - Gene Expression Regulation, Neoplastic KW - Humans KW - Immunoprecipitation KW - In Situ Hybridization, Fluorescence KW - In Vitro Techniques KW - Lung Neoplasms KW - Mice KW - NIH 3T3 Cells KW - Nuclear Proteins KW - Polymorphism, Genetic KW - Protein Binding KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Small Interfering KW - Sequence Analysis, DNA KW - Transcription Factors KW - Tumor Suppressor Proteins AB -

Protein kinase CK2 is frequently up-regulated in human cancers, although the mechanism of CK2 activation in cancer remains unknown. In this study, we investigated the role of the CK2alpha intronless gene (CSNK2A1P, a presumed CK2alpha pseudogene) in the pathogenesis of human cancers. We found evidence of amplification and over-expression of the CSNK2A1P gene in non-small cell lung cancer and leukemia cell lines and 25% of the lung cancer tissues studied. The mRNA expression levels correlated with the copy numbers of the CSNK2A1P gene. We also identified a novel polymorphic variant (398T/C, I133T) of the CSNK2A1P gene and showed that the 398T allele is selectively amplified over the 398C allele in 101 non-small cell lung cancer tissue samples compared to those in 48 normal controls (p = 0.013<0.05). We show for the first time CSNK2A1P protein expression in transfected human embryonic kidney 293T and mouse embryonic fibroblast NIH-3T3 cell lines. Both alleles are transforming in these cell lines, and the 398T allele appears to be more transforming than the 398C allele. Moreover, the 398T allele degrades PML tumor suppressor protein more efficiently than the 398C allele and shows a relatively stronger binding to PML. Knockdown of the CSNK2A1P gene expression with specific siRNA increased the PML protein level in lung cancer cells. We report, for the first time, that the CSNK2A1P gene is a functional proto-oncogene in human cancers and its functional polymorphism appears to degrade PML differentially in cancer cells. These results are consistent with an important role for the 398T allele of the CSNK2A1P in human lung cancer susceptibility.

VL - 5 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20625391?dopt=Abstract ER -