PRC17, a novel oncogene encoding a Rab GTPase-activating protein, is amplified in prostate cancer

Pei, L., Peng, Y., Yang, Y., Ling, X. B., Van Eyndhoven, W. G., Nguyen, K. C., Rubin, M., Hoey, T., Powers, S., Li, J. (October 2002) PRC17, a novel oncogene encoding a Rab GTPase-activating protein, is amplified in prostate cancer. Cancer Res, 62 (19). pp. 5420-4. ISSN 0008-5472 (Print)0008-5472

URL: http://www.ncbi.nlm.nih.gov/pubmed/12359748

Abstract

We used cDNA-based genomic microarrays to examine DNA copy number changes in a panel of prostate tumors and found a previously undescribed amplicon on chromosome 17 containing a novel overexpressed gene that we termed prostate cancer gene 17 (PRC17). When overexpressed in 3T3 mouse fibroblast cells, PRC17 induced growth in low serum, loss of contact inhibition, and tumor formation in nude mice. The PRC17 gene product contains a GTPase-activating protein (GAP) catalytic core motif found in various Rab/Ypt GAPs, including RN-Tre. Similar to RN-Tre, we found that PRC17 protein interacts directly with Rab5 and stimulates its GTP hydrolysis. Point mutations that alter conserved amino acid residues within the PRC17 GAP domain abolished its transforming abilities, suggesting that GAP activity is essential for its oncogenic function. Whereas PRC17 is amplified in 15% of prostate cancers, it is highly overexpressed in approximately one-half of metastatic prostate tumors. The potent oncogenic activity of PRC17 is likely to influence the tumorigenic phenotype of these prostate cancers.

Item Type: Paper
Uncontrolled Keywords: 3T3 Cells Amino Acid Sequence Animals Cell Division/genetics Chromosomes, Human, Pair 17/genetics Enzyme Activation GTPase-Activating Proteins/*genetics/metabolism Gene Amplification Humans Male Mice Mice, Nude Molecular Sequence Data Oligonucleotide Array Sequence Analysis Oncogene Proteins/*genetics/metabolism Prostatic Neoplasms/*genetics/metabolism Proto-Oncogene Proteins Sequence Homology, Amino Acid Tumor Cells, Cultured rab5 GTP-Binding Proteins/metabolism
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
diseases & disorders > cancer > cancer types > prostate cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein > Rab
CSHL Authors:
Communities: CSHL labs > Powers lab
Depositing User: Matt Covey
Date: 1 October 2002
Date Deposited: 25 Feb 2014 16:05
Last Modified: 25 Feb 2014 16:05
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29532

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving