Cyclin D1 splice variants: polymorphism, risk, and isoform-specific regulation in prostate cancer.

ABSTRACT:

Purpose

Alternative CCND1 splicing results in cyclin D1b, which has specialized, protumorigenic functions in prostate not shared by the cyclin D1a (full length) isoform. Here, the frequency, tumor relevance, and mechanisms controlling cyclin D1b were challenged.

Experimental design

First, relative expression of both cyclin D1 isoforms was determined in prostate adenocarcinomas. Second, relevance of the androgen axis was determined. Third, minigenes were created to interrogate the role of the G/A870 polymorphism (within the splice site), and findings were validated in primary tissue. Fourth, the effect of G/A870 on cancer risk was assessed in two large case-control studies.

Results

Cyclin D1b is induced in tumors, and a significant subset expressed this isoform in the

SUBMITTER: Comstock CE 

PROVIDER: S-EPMC2849314 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature