Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer.

Abstract:

:The cyclin-dependent kinase (CDK) inhibitor p18 blocks progression of the cell cycle by associating with the cyclin D-dependent kinases CDK6 and CDK4. To better understand the regulation of p18 gene expression, we isolated full-length cDNA clones from a human BT-20 breast cancer cell cDNA library. These clones were then used to isolate the human gene from a human genomic DNA library. The human p18 gene spans at least 7.5 kb and is composed of three exons, two of which encode the p18 protein. The genomic clone we isolated contained 5 kb of putative promotor sequence which directed expression of the luciferase reporter gene in transient transfection experiments. The longest cDNA that we isolated from BT-20 cells contained 2103 nucleotides which corresponds to the size of the major RNA transcript detected by Northern analysis in these cells. Transcription start sites mapping to the 5' end of the putative full-length cDNA were identified by ribonuclease protection assays. A novel polymorphism was identified in the 3' untranslated region of BT-20 cell cDNA clones that contained the previously described codon 72 mutation. The codon 72 mutation was also detected in 3 of 35 breast tumors analyzed using a mismatch PCR/RFLP strategy.

authors

Blais A,Labrie Y,Pouliot F,Lachance Y,Labrie C

doi

10.1006/bbrc.1998.8497

subject

Has Abstract

pub_date

1998-06-09 00:00:00

pages

146-53

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)98497-2

journal_volume

247

pub_type

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