OVEREXPRESSION OF C-ERBB-2 AND C-MYC BUT NOT C-RAS, IN CANINE MELANOMA CELL-LINES, IS ASSOCIATED WITH METASTATIC POTENTIAL IN NUDE-MICE

Overexpression of the proto-oncogenes c-erbB-2, c-myc, and c-ras have been associated with neoplastic transformation in a variety of tumours . We investigated expression of these oncogenes in 5 canine melanoma c ell lines and 6 clonal derivatives of 1 of the cell lines, CML-6M, to determine what impact overexpression had on tumour cell growth and met astatic potential. All 11 cell lines were tumourigenic at subcutaneous inoculation sites in nude mice, but spontaneous metastasis to lung wa s a characteristic of only the CML-6M cell line and 3 of 6 clonal deri vatives of CML-6M. Investigation of oncogene overexpression revealed n o obvious pattern of expression among the 5 tumour-derived cell lines whereas overexpression of c-erbB-2 and 6-myc was consistently found in the 3 clonal cell lines characterized by high metastatic potential, a nd in primary and metastatic mouse xenografts induced by these lines. This data suggests involvement of overexpression of these genes in dev elopment of canine melanoma and associates their overexpression with m etastatic potential in nude mice.