Aberrant p16INK4A RNA transcripts expressed in hepatocellular carcinoma cell lines regulate pRb phosphorylation by binding with CDK4, resulting in delayed cell cycle progression

Authors

  • Jae-We Cho,

    1. Department of Microbiology, College of Medicine, Seonam University, 720 Kwangchi-Dong, Namwon, Chunpook 590-711, Korea,
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  • Yong-Wook Jeong,

    1. Department of Microbiology, College of Medicine, Seonam University, 720 Kwangchi-Dong, Namwon, Chunpook 590-711, Korea,
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  • Seung-Wook Han,

    1. Department of Pathology, School of Medicine, Catholic University of Daegu, 3056-6 Daemyung-Dong, Namgu, Daegu 700-718, Korea,
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  • Jae-Bok Park,

    1. Department of Pathology, School of Medicine, Catholic University of Daegu, 3056-6 Daemyung-Dong, Namgu, Daegu 700-718, Korea,
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  • Byeong-Churl Jang,

    1. Department of Microbiology and Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea,
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  • Won-Ki Baek,

    1. Department of Microbiology and Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea,
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  • Taeg Kyu Kwon,

    1. Department of Immunology and Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea, and
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  • Jong-Wook Park,

    1. Department of Immunology and Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea, and
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  • Sang-Pyo Kim,

    1. Department of Pathology, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, South Korea
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  • Min-Ho Suh,

    1. Department of Microbiology and Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea,
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  • Seong-Il Suh

    1. Department of Microbiology and Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea,
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Seong-Il Suh, Department of Microbiology, Keimyung University, School of Medicine, 194 Dongsan Dong Jung-Gu, Daegu 700-712, South Korea.
Tel: 82 53 250 7442.
Fax: 82 53 255 1398.
e-mail: seong@dsmc.or.kr

Abstract

Abstract: The inactivation of the p16INK4A (p16) gene by promoter hypermethylation has been reported in many human cancers. We previously reported that aberrant p16 RNA transcripts are expressed in hepatocellular carcinoma (HCC) cell lines having hypermethylated p16 promoters. In this study, we investigated the functional roles of aberrant p16 RNA transcripts in HCC cells to elucidate molecular events underlying hepatocarcinogenesis. The aberrant p16 RNA transcripts encoded key peptides (amino acids 84–103) involved in binding with cyclin-dependent kinase (CDK) 4. GST-aberrant p16 fusion proteins were found to interact with endogenous CDK4 in vitro. Furthermore, overexpression of these aberrant p16 RNA transcripts resulted in decreased cell proliferation rate, enlargement of cell shape and reduced level of hyperphosphorylated forms of pRb. Overall, our results suggest that the aberrant p16 RNA transcripts have functions similar to those of wild type p16 in controlling cell cycle.

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