Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-12-28
pubmed:abstractText
Aberrant cyclin expression has been implicated in oncogenesis in a number of human cancers. Since altered 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 p16INK4, p15INK4B and p21WAF1/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 p16INK4 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 p16INK4 expression vector into MDA-MB-231 cells lacking the INK4 gene failed to produce any p16INK4-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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CDKN2B protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Cyclins, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
584-91
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7591270-Base Sequence, pubmed-meshheading:7591270-Breast, pubmed-meshheading:7591270-Breast Neoplasms, pubmed-meshheading:7591270-Carrier Proteins, pubmed-meshheading:7591270-Cell Cycle Proteins, pubmed-meshheading:7591270-Cyclin-Dependent Kinase Inhibitor p15, pubmed-meshheading:7591270-Cyclin-Dependent Kinase Inhibitor p16, pubmed-meshheading:7591270-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:7591270-Cyclin-Dependent Kinases, pubmed-meshheading:7591270-Cyclins, pubmed-meshheading:7591270-Enzyme Inhibitors, pubmed-meshheading:7591270-Female, pubmed-meshheading:7591270-Gene Deletion, pubmed-meshheading:7591270-Gene Expression, pubmed-meshheading:7591270-Humans, pubmed-meshheading:7591270-Molecular Sequence Data, pubmed-meshheading:7591270-Mutation, pubmed-meshheading:7591270-RNA, Messenger, pubmed-meshheading:7591270-Tumor Cells, Cultured, pubmed-meshheading:7591270-Tumor Suppressor Proteins
pubmed:year
1995
pubmed:articleTitle
Expression of the cyclin-dependent kinase inhibitors p16INK4, p15INK4B and p21WAF1/CIP1 in human breast cancer.
pubmed:affiliation
Cancer Biology Division, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, NSW, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't