Mechanisms of human melanoma cell growth and tumor suppression by chromosome 6.

Abstract

Breaks and deletions of chromosome 6 are among the most frequent karyotypic abnormalities that appear in human malignant melanoma cells, and chromosome transfer experiments have provided functional evidence for the presence of a melanoma tumor suppressor locus on chromosome 6[J.M. Trent et al., Science (Washington DC), 247: 568-571, 1990]. We have investigated the genetic mechanism of this suppression. We have found that the suppression of tumorigenicity that follows the introduction of a normal copy of chromosome 6 into the UACC 903 human melanoma cell line is correlated with increased chromosome 6 dosage, rather than with the presence of the transferred normal copy of the chromosome. Transfer of chromosome 6 into another human melanoma cell line, MelJuSo, does not result in suppression of primary tumor formation, although the additional copy of chromosome 6 does reduce the cell growth rate in vitro. Finally, we have identified a substantial portion of the chromosome that is evidently not involved in tumor suppression. We have observed that a copy of chromosome 6 derived from a normal cell but with a deletion involving chromosome bands 6q22-6q24 suppresses primary tumor formation in UACC 903 cells as effectively as the intact chromosome. We have thus provided additional information about the chromosomal location of this tumor suppressor and about its mode of action.