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The p44S10 locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma

Oncogene volume 19, pages 1419–1427 (2000)Cite this article

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 p44S10, a highly conserved subunit of the 26S proteasome that exhibits similarity to the Arabidopsis fus6/cop11 family of signaling molecules. p44S10 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 p44S10, and increased expression of p44S10 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.

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Acknowledgements

Tissue was obtained through the Tissue Procurement Facility of the University of Alabama at Birmingham Comprehensive Cancer Center and the Cooperative Human Tissue Network. Funded by NIH grants R29CA65686 (JM Ruppert) and CA48031 (N-d Wang and DI Smith), a Jr. Faculty Award through the Comprehensive Cancer Center (JMR), and grants from the Medical Research Council of Canada (Y Ben-David).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA

    Songrong Ren, Iuri D Louro & J Michael Ruppert

  2. Division of Hematology/Oncology, Department of Medicine, and the Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA

    Martin J Smith, Peggy McKie-Bell, David T Redden & J Michael Ruppert

  3. Sunnybrook Health Sciences Center and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    Maria Rosa Bani, Miriam Wagner, Barry Zochodne & Yaacov Ben-David

  4. Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA

    William E Grizzle

  5. Department of Laboratory Medicine and Pathology, Mayo Foundation, Rochester, Minnesota, USA

    Nai-dy Wang & David I Smith

  6. Department of Dermatology, Hannover Medical School, Ricklinger Strasse 5, D 30449 Hannover, Germany

    Rudolph A Herbst

  7. Department of Medical Oncology (Cancer Research), University of Essen Medical School, West German Cancer Center Essen, 45122 Essen, Germany

    Walter Bardenheuer, Bertram Opalka & Jochen Schütte

  8. National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA

    Jeffrey M Trent

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  1. Songrong Ren
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Ren, S., Smith, M., Louro, I. et al. The p44S10 locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma. Oncogene 19, 1419–1427 (2000). https://doi.org/10.1038/sj.onc.1203462

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  • DOI: https://doi.org/10.1038/sj.onc.1203462

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