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


RESULTS
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.
Farina
Anne K
AK
Departments of Oncology and Biochemistry, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, United States of America.
Bong
Yong-Sik
YS
Feltes
Carolyn M
CM
Byers
Stephen W
SW
D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis; D051176:beta Catenin / Q000502:physiology*
D020413:3' Untranslated Regions; D015820:Cadherins; D012333:RNA, Messenger; D051176:beta Catenin; C086960:osteoblast cadherin; D038362:Glycogen Synthase Kinase 3