BRK/Sik Expression in the Gastrointestinal Tract and in Colon Tumors

Clones encoding the breast tumor kinase BRK were isolated from a normal human small intestinal cDNA library that was screened with the cDNA encoding the mouse epithelial-specific tyrosine kinase Sik. Although BRK and Sik share only 80% amino acid sequence identity, Southern blot hybridizations confi...

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Bibliographic Details
Published in:Clinical cancer research 1999-07, Vol.5 (7), p.1767-1777
Main Authors: LLOR, X, SERFAS, M. S, WENJUN BIE, VASIOUKHIN, V, POLONSKAIA, M, DERRY, J, ABBOTT, C. M, TYNER, A. L
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Biological and medical sciences
Biomarkers, Tumor - biosynthesis
Caco-2 Cells
Chromosomes, Human, Pair 20
Colonic Neoplasms - chemistry
Colonic Neoplasms - metabolism
Digestive System - metabolism
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Medical sciences
Mice
Molecular Sequence Data
Neoplasm Proteins
Protein-Tyrosine Kinases - biosynthesis
Protein-Tyrosine Kinases - chemistry
Protein-Tyrosine Kinases - genetics
Sequence Homology, Amino Acid
src-Family Kinases - biosynthesis
src-Family Kinases - chemistry
src-Family Kinases - genetics
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumor Cells, Cultured
Tumors
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Summary:Clones encoding the breast tumor kinase BRK were isolated from a normal human small intestinal cDNA library that was screened with the cDNA encoding the mouse epithelial-specific tyrosine kinase Sik. Although BRK and Sik share only 80% amino acid sequence identity, Southern blot hybridizations confirmed that the two proteins are orthologues. Sik was mapped to mouse distal chromosome 2, which shows conservation of synteny with human chromosome 20q13.3, the location of the BRK gene. BRK expression was examined in the normal gastrointestinal tract, colon tumor cell lines, and primary colon tumor samples. Like Sik, BRK is expressed in normal epithelial cells of the gastrointestinal tract that are undergoing terminal differentiation. BRK expression also increased during differentiation of the Caco-2 colon adenocarcinoma cell line. Modest increases in BRK expression were detected in primary colon tumors by RNase protection, in situ hybridization, and immunohistochemical assays. The BRK tyrosine kinase appears to play a role in signal transduction in the normal gastrointestinal tract, and its overexpression may be linked to the development of a variety of epithelial tumors.
ISSN:1078-0432
1557-3265