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Expression of the cyclin‐dependent kinase inhibitors p16 INK4 , p15 INK4B and p21Waf1/cip1 in human breast cancer
Author(s) -
Musgrove Elizabeth A.,
Liuschkis Richard,
Cornish Ann L.,
Lee Christine S. L.,
Setlur Vittal,
Seshadri Ram,
Sutherland Robert L.
Publication year - 1995
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/ijc.2910630420
Subject(s) - biology , cyclin dependent kinase , cancer research , carcinogenesis , tumor suppressor gene , retinoblastoma , cyclin dependent kinase 4 , retinoblastoma protein , cyclin dependent kinase 6 , cdk inhibitor , cyclin d1 , cell cycle , kinase , cell culture , microbiology and biotechnology , gene , cyclin dependent kinase 2 , genetics
Ahderrant cyclin expression has been implicated in oncogenesis in a number of human cancers. Since alterehd function of regulators of cyclin‐dependent kinase (CDK) activity other than cyclins, in particular CDK inhibitors, might play a similar role in oncogenesis, we examined the expression and regulation of the CDK inhibitors p16 INk4 p15 INK4B and p21 WAF1/CIP1 in human breast cancer cell lines. Both the INK4 and INK4B genes were homozygously deleted in 3 cell lines, while INK4 alone was deleted in 2 cell lines. A further 2 cell lines displayed loss of an allele at this locus, and in 1 of these the remaining allele contained a mis‐sense mutation within the coding region of the p16 INK4 protein. The majority of cell lines examined, including 2 normal mammary epithelial cell strains, expressed low levels of INK4 mRNA and low or undetectable levels of INK4B mRNA. However, INK4 mRNA was expressed at high levels in 5 cell lines, and this was associated with deletion or inactivation of the retinoblastoma susceptibility gene product pRB but not with mutation of TP53 . No deletions of the WAF1/CIP1 gene were observed, but WAF1/CIP1 mRNA levels were reduced in cell lines with TP53 mutation. Transfection of a p16 INK4 expression vector into MDA‐MB‐231 cells lacking the INK4 gene failed to produce any p16 INK4 ‐expressing cell lines, suggesting that such cells were selected against in continuous culture. Despite the frequent deletion of INK4 in breast cancer cell lines, no evidence was obtained for INK4 deletions in DNA from 45 primary breast carcinomas. Thus, homozygous deletion of the INK4 gene appears to be a rare event in primary breast cancer.