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
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: |
https://repository.cshl.edu/id/eprint/29532 |
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