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Aberrant Transcripts of the Cyclin-dependent Kinase-associated Protein Phosphatase in Hepatocellular Carcinoma¹

Liver Research Unit [C-T. Y., S-C. L., C-Y. P., Y-F. L.] and Department of Pathology [T-C. C.], Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan

The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner. To investigate whether mutations of this enzyme occur in hepatocellular carcinoma (HCC), KAP mRNA was analyzed by reverse transcription-PCR (RT-PCR), followed by cloning and sequencing. Eight of 14 biopsy tissues obtained from advanced HCC, 6 of 13 surgically removed HCC tissues, and 2 of the adjacent noncancerous tissues contained aberrant KAP transcripts. Using the yeast two-hybrid system, five of seven representative KAP mutants were shown to be defective in interacting with Cdk2. These data suggest a possible role of KAP mutations in multiple-step hepatocarcinogenesis.

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