BRK/Sik expression in the gastrointestinal tract and in colon tumors

Clones encoding the breast tumor kinase BRK were isolated from a normal hum an small intestinal cDNA library that was screened with the cDNA encoding t he mouse epithelial-specific tyrosine kinase Sik, Although BRK and Sik shar e only 80% amino acid sequence identity, Southern blot hybridizations confi rmed that the two proteins are orthologues, Sik was mapped to mouse distal chromosome 2, which shows conservation of synteny with human chromosome 20q 13.3, the location of the BRK gene. BRK expression was examined in the norm al gastrointestinal tract, colon tumor cell lines, and primary colon tumor samples. Like Sik, BRK is expressed in normal epithelial cells of the gastr ointestinal tract that are undergoing terminal differentiation. BRK express ion also increased during differentiation of the Caco-2 colon adenocarcinom a cell line. Modest increases in BRK expression were detected in primary co lon tumors by RNase protection, in situ hybridization, and immunohistochemi cal assays. The BRK tyrosine kinase appears to play a role in signal transd uction in the normal gastrointestinal tract, and its overexpression may be linked to the development of a variety of epithelial tumors.