The p44(S10) locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma

Songrong Ren, Martin J. Smith, Iuri D. Louro, Peggy McKie-Bell, Maria Rosa Bani, Miriam Wagner, Barry Zochodne, David T. Redden, William E. Grizzle, Nai Dy Wang, David I. Smith, Rudolph A. Herbst, Walter Bardenheuer, Bertram Opalka, Jochen Schütte, Jeffrey M. Trent, Yaacov Ben-David, J. Michael Ruppert, M. Negri

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Gene amplification is frequently present in human tumors, although specific target genes relevant to many amplified loci remain unidentified. An expression cloning assay enabled identification of a candidate oncogene derived from human chromosome 3p14.1. The cDNA retrieved from morphologically transformed cells contained the full-length protein coding region and detected an abundant transcript in the same cells. Sequence analysis revealed identity with the wild-type sequence of p44(S10), a highly conserved subunit of the 26S proteasome that exhibits similarity to the Arabidopsis fus6/cop11 family of signaling molecules. p44(S10) gene copy number and mRNA expression were increased in association with segmental 1.8-11-fold chromosomal gains in cutaneous malignant melanoma cell lines (5/13; 40%) and tumors (2/40; 5%), and in breast cancer MCF-7 cells. Likewise, malignant progression of human radial growth phase WM35 melanoma cells was associated with amplification and increased expression of endogenous p44(S10), and increased expression of p44(S10) was sufficient to induce proliferation of WM35 cells in vivo. The results demonstrate segmental copy number gains within chromosome 3p in cutaneous malignant melanoma and suggest that deregulation of a proteasome regulatory particle subunit may contribute to the malignant phenotype.

Original languageEnglish (US)
Pages (from-to)1419-1427
Number of pages9
JournalOncogene
Volume19
Issue number11
DOIs
StatePublished - Mar 9 2000

Keywords

  • Gene amplification
  • Melanoma
  • Proteasome
  • Regulatory particle
  • p44(S10)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Ren, S., Smith, M. J., Louro, I. D., McKie-Bell, P., Bani, M. R., Wagner, M., Zochodne, B., Redden, D. T., Grizzle, W. E., Wang, N. D., Smith, D. I., Herbst, R. A., Bardenheuer, W., Opalka, B., Schütte, J., Trent, J. M., Ben-David, Y., Ruppert, J. M., & Negri, M. (2000). The p44(S10) locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma. Oncogene, 19(11), 1419-1427. https://doi.org/10.1038/sj.onc.1203462