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Overexpression of ERK, an EPH Family Receptor Protein Tyrosine Kinase, in Various Human Tumors¹

First Department of Pathology, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-31 [E. K., M. T., T. I., M. S., Y-y. X., Y. N., H. S., I. K.], and Department of Genetics, Research Institute International Medical Center of Japan [S. T., K. Y.], Japan

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) encompassing the catalytic domain of ERK from the expression library of human gastric cancer with an antiphosphotyrosine antibody. Using this cDNA as a probe, the cDNAs encoding mature ERK protein were isolated. The putative mature ERK protein, a total of 967 deduced amino acid residues, showed high homology with chicken Cek5 (92.5%) and mouse Nuk (99.1%). Chromosomal in situ hybridization revealed that human ERK cDNA is localized to chromosome 1p34–35. In Northern blot analysis of normal human tissues, the ERK gene was ubiquitously expressed mainly in cells of epithelial origin but not in the brain. Studies on RNAs from 76 human tumor tissues and cell lines showed that ERK is expressed at higher levels in various tumors of epithelial origin than in corresponding normal tissues, most frequently in gastric cancers (12 of 16, 75.0%). Overexpression of ERK was also detected in one osteosarcoma cell line. These findings suggest that ERK plays some significant role in carcinogenesis in the stomach and other tissues.

¹ This work was supported in part by the Smoking Research Foundation, the Ministry of Education, Culture and Science of Japan (05151015, 05151023, 05151025), and the Ministry of Health and Welfare of Japan. M. T. is the recipient of a fellowship from the Japan Society for Promotion of Science for Junior Scientists.

² To whom requests for reprints should be addressed.

Received 3/23/94. Accepted 5/26/94.

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