title: Frequent activation of the β-catenin gene in sporadic colorectal carcinomas: A mutational & expression analysis.
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.
authors.affiliation: Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.|Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Mumtaz
authors.initials: M
authors.lastname: Anwar
authors.affiliation: Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kochhar
authors.affiliation: Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Rajinder
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Alka
authors.initials: A
authors.lastname: Bhatia
authors.affiliation: Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Kim
authors.initials: K
authors.lastname: Vaiphei
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh, India.
authors.forename: Akhtar
authors.initials: A
authors.lastname: Mahmood
authors.affiliation: Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. mahmoodpgi@gmail.com.
authors.forename: Safrun
authors.initials: S
authors.lastname: Mahmood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin
keywords: beta-catenin; colorectal cancer; expression histopathology; gene mutation