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PLoS One. 2009;4(3):e4797. doi: 10.1371/journal.pone.0004797. Epub 2009 Mar 10.

Post-transcriptional regulation of cadherin-11 expression by GSK-3 and beta-catenin in prostate and breast cancer cells.

Author information

1
Departments of Oncology and Biochemistry, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, United States of America.

Abstract

BACKGROUND:

The cell-cell adhesion molecule cadherin-11 is important in embryogenesis and bone morphogenesis, invasion of cancer cells, lymphangiogenesis, homing of cancer cells to bone, and rheumatoid arthritis. However, very little is known about the regulation of cadherin-11 expression.

METHODOLOGY/PRINCIPAL FINDINGS:

Here we show that cell density and GSK-3beta regulate cadherin-11 levels in cancer cells. Inactivation of GSK3beta with lithium chloride or the GSK3 inhibitor BIO and GSK3beta knockdown with siRNA repressed cadherin-11 mRNA and protein levels. RNA Polymerase II chromatin immunoprecipitation experiments showed that inhibition of GSK3 does not affect cadherin-11 gene transcription. Although the cadherin-11 3'UTR contains putative microRNA target sites and is regulated by Dicer, its stability is not regulated by GSK3 inhibition or density. Our data show that GSK3beta regulates cadherin-11 expression in two ways: first a beta-catenin-independent regulation of cadherin-11 steady state mRNA levels, and second a beta-catenin-dependent effect on cadherin-11 3'UTR stability and protein translation.

CONCLUSIONS:

Cadherin-11 mRNA and protein levels are regulated by the activity of GSK3beta and a significant degree of this regulation is exerted by the GSK3 target, beta-catenin, at the level of the cadherin-11 3'UTR.

PMID:
19274078
PMCID:
PMC2650783
DOI:
10.1371/journal.pone.0004797
[Indexed for MEDLINE]
Free PMC Article

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