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 lines C8161 and MelJuSo suppresses metastasis by at least 95% without affecting tumorigenicity. Subtractive hybridization and differential display were used to identify the molecule(s) responsible for suppressing metastasis in neo6/melanoma (neo6/C8161 and neo6/MelJuSo) hybrids. Seven cDNA clones exhibiting quantitatively or qualitatively higher expression in neo6/melanoma hybrids were obtained. These genes fell into 2 categories: 1) transcription-related genes (AP-2A, HMG-I(Y) and a novel 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-1, significantly suppressed metastasis of the human malignant melanoma cell lines MelJuSo and a highly metastatic subclone of C8161, C8161cl.9, following transfection and constitutive expression. Our results illustrate the power of subtractive hybridization and differential display to identify functional metastasis-controlling genes in human melanoma.
Lee
J H
JH
The Jake Gittlen Cancer Research Institute, Pennsylvania State University College of Medicine, Hershey 17033-0850, USA.
Welch
D R
DR
D000595:Amino Acid Sequence; D001483:Base Sequence; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D018076:DNA, Complementary; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D006822:Hybrid Cells; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D000090243:Nucleophosmin; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin