A Novel Tyrosine Kinase Expressed in Breast Tumors.
Annual rept. 19 Aug 97-18 Aug 98
ILLINOIS UNIV AT CHICAGO
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The breast tumor kinase BRK was isolated from a normal human small intestinal cDNA library that was screened with the cDNA encoding the mouse epithelial specific tyrosine kinase 51K. While BRK and 51K share only 80 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 where the BRK gene is located. Chromosome 20q13 is frequently amplified in a number of tumor types, including breast and colon tumors. Increased BRK expression has been detected in a high proportion of human breast tumors. However, when 51K expression was examined at different stages of normal mammary gland differentiation in the mouse, no expression was detected. Overexpression of wildtype SIK in the normal murine mammary gland cell line NMuMG did not result in increased cell proliferation or foci formation. We are in the process of comparing the activities of SIK and BRK, and determining what growth factors may regulate this epithelial cell specific tyrosine kinase. SIKBRK appears to play a role in signal transduction in the normal gastrointestinal tract, and its overexpression may be linked to the development of breast and colon tumors.
- Medicine and Medical Research