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

• Published in: Oncogene Vol. 19; no. 11; pp. 1419 - 1427
• Main Authors: SONGRONG REN, SMITH, M. J, SMITH, D. I, HERBST, R. A, BARDENHEUER, W, OPALKA, B, SCHÜTTE, J, TRENT, J. M, BEN-DAVID, Y, RUPPERT, J. M, LOURO, J. D, MCKIE-BELL, P, BANI, M. R, WAGNER, M, ZOCHODNE, B, REDDEN, D. T, GRIZZLE, W. E, WANG, N.-D
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 09-03-2000; Nature Publishing Group
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - isolation & purification; Animals; Biological and medical sciences; Breast cancer; Cell Line, Transformed; Cell physiology; Cell proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosome 3; Chromosomes; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 20; Chromosomes, Human, Pair 3; Conserved sequence; Copy number; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - isolation & purification; Cysteine Endopeptidases - metabolism; Disease Progression; Enzyme Activation - genetics; Fundamental and applied biological sciences. Psychology; Gene Amplification; Gene expression; Genes; Humans; Medical research; Melanoma; Melanoma - enzymology; Melanoma - genetics; Melanoma - pathology; Melanoma, Experimental - enzymology; Melanoma, Experimental - genetics; Melanoma, Experimental - pathology; Mice; Mice, Nude; Molecular and cellular biology; Molecular Sequence Data; Multienzyme Complexes - genetics; Multienzyme Complexes - isolation & purification; Multienzyme Complexes - metabolism; Oncogene Proteins - genetics; Oncogene Proteins - isolation & purification; Oncogene Proteins - metabolism; Oncology; Peptide Hydrolases - genetics; Peptide Hydrolases - isolation & purification; Peptide Hydrolases - metabolism; Phenotypes; Proteasome 26S; Proteasome Endopeptidase Complex; Rats; Sequence analysis; Sequence Analysis, DNA; Skin cancer; Skin Neoplasms - enzymology; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Transcription; Transformed cells; Tumor Cells, Cultured; Tumors; Alabama; United States > US; Germany; Human; Multicatalytic endopeptidase complex; Targeting; Nucleotide sequence; Enzyme; Chromosome A3; Regulatory subunit; Malignant tumor; Gene expression; Particle; Peptidases; Signal transduction; Gene amplification; Regulation(control); Cell line; Complementary DNA; C-Onc gene; Malignant melanoma; Tumor progression; Hydrolases; Physical map
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203462

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.