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Molecular analysis of the cyclin‐dependent kinase inhibitor genes p15 INK4b/MTS21 , p16 INK4/MTS1 , p18 and pl9 in human cancer cell lines
Author(s) -
Gemma Akihiko,
Takenoshita Seiichi,
Hagiwara Koichi,
Okamoto Aikou,
Spillare Elisa A.,
McMemamin Mary G.,
Hussain S. Perwez,
Forrester Kathleen,
Zariwala Maimoona,
Xiong Yue,
Harris Curtis C.
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19961127)68:5<605::aid-ijc9>3.0.co;2-2
Subject(s) - biology , gene , tumor suppressor gene , genetics , exon , cyclin dependent kinase 4 , cell cycle , cancer , cancer research , microbiology and biotechnology , carcinogenesis , cyclin dependent kinase 2
Cyclin‐dependent kinase‐4 inhibitor genes (INK4) regulate the cell cycle and are candidate tumor‐suppressor genes. To determine if alterations in the coding regions of the pl8 and pl9 genes, which are novel members of the INK4 family and if they correlate with the development of human cancer, 100 human cancer cell lines were analyzed. Two other INK4 gene family members, p15 INK4b/MTS2 and pl6 INK4/MTS1 genes were also analyzed. Homozygous deletions of the p15 INK4b/MTS2 gene were detected in 29 cancer cell lines. Thirty‐five homozygous deletions and 7 intragenic mutations of the pl6 INK4/MTS1 gene were also detected in these cell lines. Neither homozygous deletions nor intragenic mutations of the p18 and p19 genes were found except in an ovarian cancer cell line, SKOV3, harboring a single base pair deletion in exon 1 of p19 . In p16 INK4/MTS1 expression analysis, 5 cell lines with both authentic and alternative spliced pl6 INK4/MTS1 mRNA had no detectable pl6 INK4/MTS1 protein. These results suggest the hypotheses that either post‐translational modification or enhanced degradation may be responsible for the lack of detection of the pl6 INK4/MTS1 protein. Using Western blot analysis, subsets of 26 human cancer cell lines were examined for pl8 expression and 39 cell lines for p19 expression. All of these cell lines expressed the pl8 or pl9 protein, with the exception of SKOV3, which did not express pl9 . Therefore, the INK4 gene family may be divided into 2 groups. One group includes p15 INK4b/MTS2 and pl6 INK4/MTS1 in which genetic and epigenetic alterations might contribute to the development of human cancers. The other group includes p18 and p19 , in which somatic mutations are uncommon in many types of human cancer, and their role in human carcinogenesis and cancer progression is uncertain. (This article is a US Government work and, as such, is in the public domain in the United States of America.) © 1996 Wiley‐Liss, Inc.