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Protein B61 as a New Growth Factor: Expression of B61 and Up-Regulation of Its Receptor Epithelial Cell Kinase during Melanoma Progression¹

St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE [D. J. E., K. M., D. C. B.] and Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH [C. J. F.], United Kingdom; AMGEN, AMGEN Center, Thousand Oaks, California 91320-1789 [B. A. G., R. A. L., R. J. T.]; and the Wistar Institute, Philadelphia, Pennsylvania 19104 [M. H.]

Epithelial cell kinase (ECK) is a receptor protein tyrosine kinase, the role of which in melanoma biology is unclear. Here we studied the role of ECK during melanoma progression. ECK mRNA was overexpressed in virtually all melanoma lines tested, and levels were significantly higher in cell lines from distant metastases than primary melanomas; melanocytes were negative. Gene amplification was not detected in melanomas. Levels of ECK protein corresponded well with mRNA levels. B61 or LERK-1, recently identified as an ECK ligand, stimulated the growth of ECK-expressing melanoma cell lines, its first identified biological activity. Melanoma chemotaxis and chemoinvasion were not affected by B61. Growth of normal melanocytes was not affected. mRNA for B61 was detected in both melanoma cell lines and normal melanocytes. B61 was also identified by Western blotting and ECK binding activity with the use of a BIAcore binding assay in melanoma cell-conditioned media. These results suggest that B61 is an autocrine growth factor for melanomas but not normal melanocytes.

¹ This work was supported by Cancer Research Campaign Grant SP1923/0501.

² To whom requests for reprints should be addressed.

Received 4/ 3/95. Accepted 5/ 4/95.

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