Identification of highly expressed genes in metastasis-suppressed chromosome 6/human malignant melanoma hybrid cells using subtractive hybridization and differential display

Int J Cancer. 1997 Jun 11;71(6):1035-44. doi: 10.1002/(sici)1097-0215(19970611)71:6<1035::aid-ijc20>3.0.co;2-b.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Chromosomes, Human, Pair 6*
  • Cloning, Molecular
  • DNA, Complementary
  • Gene Expression*
  • Genes, Tumor Suppressor*
  • Humans
  • Hybrid Cells
  • Melanoma / genetics*
  • Melanoma / pathology
  • Molecular Sequence Data
  • Neoplasm Metastasis / genetics*
  • Nuclear Proteins / genetics
  • Nucleic Acid Hybridization
  • Tumor Cells, Cultured

Substances

  • DNA, Complementary
  • Nuclear Proteins
  • nucleophosmin