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Upregulation of glycogen synthase kinase 3ß in human colorectal adenocarcinomas correlates with accumulation of CTNNB1.

Authors: Wang, Hanlin L  Hart, John  Fan, Lifang  Mustafi, Reba  Bissonnette, Marc 
Citation: Wang HL, etal., Clin Colorectal Cancer. 2011 Mar 1;10(1):30-6. doi: 10.3816/CCC.2011.n.004.
Pubmed: (View Article at PubMed) PMID:21609933
DOI: Full-text: DOI:10.3816/CCC.2011.n.004


INTRODUCTION: Mutations of the adenomatous polyposis coli (APC) tumor suppressor gene or the CTNNB1 protooncogene have been implicated in the initiation of most human colorectal epithelial neoplasms. Glycogen synthase kinase 3ß (GSK3B) serves a critical role in regulating their functions by phosphorylating both APC and CTNNB1 to facilitate CTNNB1 degradation. The current studies were performed to investigate whether GSK3B itself is regulated during the process of colorectal tumorigenesis.
PATIENTS AND METHODS: We examined the expression of GSK3B and CTNNB1 in tissue samples from 24 human colorectal adenocarcinomas by Western immunoblotting analysis, kinase activity assays and immunohistochemistry. Normal colonic mucosa from the same colectomy specimens were used as a reference for comparison.
RESULTS: We demonstrated that GSK3B expression levels and kinase activities were markedly and significantly increased in colorectal adenocarcinomas in all 24 cases compared with paired adjacent normal-appearing colonic mucosa. These increases correlated with significantly increased expression of CTNNB1 in the same tumors. Similar results were obtained in several cultured human colon cancer cell lines, demonstrating GSK3B levels correlated with CTNNB1 expression.
CONCLUSION: Though APC and CTNNB1 regulation by GSK3B are frequently disrupted by mutations in colon cancers, our observations suggest that increased functional GSK3B might drive other growth-promoting signals in colorectal tumorigenesis.

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CRRD Object Information
CRRD ID: 13210767
Created: 2017-09-07
Species: All species
Last Modified: 2017-09-07
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.