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Aberrant p16 INK4A RNA transcripts expressed in hepatocellular carcinoma cell lines regulate pRb phosphorylation by binding with CDK4, resulting in delayed cell cycle progression
Author(s) -
Cho JaeWe,
Jeong YongWook,
Han SeungWook,
Park JaeBok,
Jang ByeongChurl,
Baek WonKi,
Kwon Taeg Kyu,
Park JongWook,
Kim SangPyo,
Suh MinHo,
Suh SeongIl
Publication year - 2003
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1034/j.1600-0676.2003.00821.x
Subject(s) - biology , rna , cell cycle , cancer research , microbiology and biotechnology , cyclin d1 , cyclin dependent kinase , gene expression , gene , fusion gene , genetics
The inactivation of the p16 INK4A (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.