Aberrant p16INK4A RNA transcripts expressed in hepatocellular carcinoma cell lines regulate pRb phosphorylation by binding with CDK4, resulting in delayed cell cycle progression.
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.
Cho
Jae-We
JW
Department of Microbiology, College of Medicine, Seonam University, 720 Kwangchi-Dong, Namwon, Chunpook 590-711, Korea.
Jeong
Yong-Wook
YW
Han
Seung-Wook
SW
Park
Jae-Bok
JB
Jang
Byeong-Churl
BC
Baek
Won-Ki
WK
Kwon
Taeg Kyu
TK
Park
Jong-Wook
JW
Kim
Sang-Pyo
SP
Suh
Min-Ho
MH
Suh
Seong-Il
SI
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D019942:Genes, p16 / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D012322:RNA Precursors / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D012322:RNA Precursors; D016160:Retinoblastoma Protein; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases