OVEREXPRESSION OF ERK, AN EPH FAMILY RECEPTOR PROTEIN-TYROSINE KINASE, IN VARIOUS HUMAN TUMORS

The ERK gene has been isolated as a genomic DNA encoding a part of the receptor protein-tyrosine kinase which belongs to the EPH subfamily. We previously identified a partial complementary DNA (cDNA) encompassi ng the catalytic domain of ERK from the expression library of human ga stric cancer with an antiphosphotyrosine antibody. Using this cDNA as a probe, the cDNAs encoding mature ERK protein were isolated. The puta tive mature ERK protein, a total of 967 deduced amino acid residues, s howed high homology with chicken Cek5 (92.5%) and mouse Nuk (99.1%). C hromosomal in situ hybridization revealed that human ERK cDNA is local ized to chromosome lp34-35. In Northern blot analysis of normal human tissues, the ERK gene was ubiquitously expressed mainly in cells of ep ithelial origin but not in the brain. Studies on RNAs from 76 human tu mor tissues and cell lines showed that ERK is expressed at higher leve ls in various tumors of epithelial origin than in corresponding normal tissues, most frequently in gastric cancers (12 of 16, 75.0%). Overex pression of ERK was also detected in one osteosarcoma cell line. These findings suggest that ERK plays some significant role in carcinogenes is in the stomach and other tissues.