We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The p44<sup>S10</sup> locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma.
- Authors
Ren, Songrong; Smith, Martin J; Louro, Iuri D; McKie-Bell, Peggy; Bani, Maria Rosa; Wagner, Miriam; Zochodne, Barry; Redden, David T; Grizzle, William E; Wang, Nai-dy; Smith, David I; Herbst, Rudolph A; Bardenheuer, Walter; Opalka, Bertram; Schütte, Jochen; Trent, Jeffrey M; Ben-David, Yaacov; Ruppert, J Michael
- 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. Oncogene (2000) 19, 1419–1427.
- Subjects
GENE amplification; HUMAN chromosomes; MELANOMA
- Publication
Oncogene, 2000, Vol 19, Issue 11, p1419
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1203462