IDENTIFICATION OF HIGHLY EXPRESSED GENES IN METASTASIS-SUPPRESSED CHROMOSOME 6 HUMAN MALIGNANT-MELANOMA HYBRID-CELLS USING SUBTRACTIVE HYBRIDIZATION AND DIFFERENTIAL DISPLAY/

Microcell-mediated transfer of chromosome 6 into human melanoma cell l ines C8161 and MelJuSo suppresses metastasis by at least 95% without a ffecting tumorigenicity. Subtractive hybridization and differential di splay were used to identify the molecule(s) responsible for suppressin g metastasis in neo6/melanoma (neo6/C8161 and neo6/MeIJuSo) hybrids. S even cDNA clones exhibiting quantitatively or qualitatively higher exp ression in neo6/melanoma hybrids were obtained. These genes fell into 2 categories: I) transcription-related genes (AP-2A, HMG-I(Y) and a no vel isoform of nucleophosmin B23), which have previously been shown to regulate metastasis-associated genes; and 2) novel genes. One of the novel genes, designated KiSS-I, significantly suppressed metastasis of the human malignant melanoma cell lines MeIJuSo and a highly metastat ic subclone of C8161, C8161 cl.9, following transfection and constitut ive expression. Our results illustrate the power of subtractive hybrid ization and differential display to identify functional metastasis-con trolling genes in human melanoma. (C) 1997 Wiley-Liss, Inc.