Inactivation of p16(INK4) in hepatocellular carcinoma

Ai Min Hui, Michiie Sakamoto, Yae Kanai, Yoshinori Ino, Masahiro Gotoh, Jun Yokota, Setsuo Hirohashi

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122 Citations (Scopus)


We analyzed the p16(INK4) status of 6 hepatocellular carcinoma (HCC) cell lines and 32 primary HCC tumors, including 9 early-stage tumors, to determine whether p16(INK4) tumor-suppressor gene inactivation participates in hepatocarcinogenesis. p16(INK4) was studied at its protein level through Western blotting, at its messenger RNA (mRNA) level through reverse- transcriptase polymerase chain reaction analysis (RT-PCR) and Northern blotting, and at its genomic level through Southern blotting and PCR-single- strand conformation polymorphism analysis. The p16 protein was absent from 3 of 6 cell lines (50%) and 11 of 32 primary tumors (34%), but present in noncancerous tissues, indicating that p16(INK4) is involved in hepatocarcinogenesis. Furthermore, we suggest that the p16 protein loss may contribute to the following: (1) early-stage hepatocarcinogenesis, because it was observed in 22% of early stage tumors; and (2) tumor progression, because it occurred approximately twice as often in advanced rather than in early stage tumors (40%). It was striking that neither p16(INK4) homozygous deletion and mutation nor loss of p16(INK4) mRNA expression were observed in HCC cell lines and primary tumors, including those specimens from which the p16 protein was absent except the Li7HM cell line, in which p16(INK4) mRNA was not detected. These results suggest that p16(INK4) in HCC is inactivated predominantly by posttranscriptional regulation rather than by genomic aberrations and lack of transcription.

Original languageEnglish
Pages (from-to)575-579
Number of pages5
Issue number3
Publication statusPublished - 1996 Sept
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology


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