Frequent activation of the β‐catenin gene in sporadic colorectal carcinomas: A mutational & expression analysis. Issue 11 (16th September 2015)

• Record Type: Journal Article
• Authors: Anwar, Mumtaz; Kochhar, Rakesh; Singh, Rajinder; Bhatia, Alka; Vaiphei, Kim; Mahmood, Akhtar; Mahmood, Safrun
• Is Part Of: Molecular carcinogenesis. Volume 55:Issue 11(2016:Nov.)
• Page Start: 1627
• Page End: 1638
• Publication Date: 2015-09-16
• Subjects: colorectal cancer -- gene mutation -- beta‐catenin -- expression histopathology; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22414
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract : β‐catenin (CTNNB1), an oncogene/onco‐protein and an adhesion molecule is a key effector in colorectal cancer (CRC). Its activation, and subsequent up‐regulation of Wnt‐signaling, is an important event in the development of certain human cancers including CRC. Mutations in the β‐catenin gene in the region of serine‐threonine glycogen kinase (GSK)‐3β phosphorylation target sites have been identified in colorectal cancer in humans. In the current study, we investigated 60 sporadic colorectal adenocarcinomas along with adjoining and normal mucosa cases in humans for β‐catenin mutations. Thirteen of sixty colorectal tumors from humans had point mutations with a frequency of 21.66% at codons 24, 26, 27, 32, 34, 35, 41, 42, 43, 46, 49, 54, 55, or 67 sites which are mutated in colorectal cancer and some of these sites in other cancers. Thus, there appears to be a key involvement of β‐catenin activation in human colorectal carcinogenesis. mRNA expression analysis using q‐Real Time PCR showed 21.5‐fold up‐regulation of β‐catenin mRNA in tumor tissue compared to normal and adjoining mucosa. Protein expression analysis using immunohistochemistry, confocal microscopy, and Western blot confirmed aberrant accumulation of β‐catenin protein along the nucleus and cytoplasm following mutation. The observed mutations and up‐regulation of mRNA in tumors, and the increased expression of β‐catenin protein in CRC suggest that these alterations are early and prognostic events in sporadic colorectal carcinogenesis in humans. © 2015 Wiley Periodicals, Inc.