Abstract
BACKGROUND. Translation of preclinical studies into effective human cancer therapy is hampered by the lack of defined molecular expression patterns in mouse models that correspond to the human counterpart. We sought to generate an open source TRAMP mouse microarray dataset and to use this array to identify differentially expressed genes from human prostate cancer (PCa) that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. METHODS. We performed microarrays on total RNA extracted and amplified from eight TRAMP tumors and nine normal prostates. A subset of differentially expressed genes was validated by QRT-PCR. Differentially expressed TRAMP genes were analyzed for concordant expression in publicly available human prostate array datasets and a subset of resulting genes was analyzed by QRT-PCR. RESULTS. Cross-referencing differentially expressed TRAMP genes to public human prostate array datasets revealed 66 genes with concordant expression in mouse and human PCa; 56 between metastases and normal and 10 between primary tumor and normal tissues. Of these 10 genes, two, Sox4 and Tubb2a, were validated by QRT-PCR. Our analysis also revealed various dysregulations in major biologic pathways in the TRAMP prostates. CONCLUSIONS. We report a TRAMP microarray dataset of which a gene subset was validated by QRT-PCR with expression patterns consistent with previous gene-specific TRAMP studies. Concordance analysis between TRAMP and human PCa associated genes supports the utility of the model and suggests several novel molecular targets for preclinical therapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1517-1530 |
| Number of pages | 14 |
| Journal | Prostate |
| Volume | 68 |
| Issue number | 14 |
| DOIs | |
| State | Published - Oct 1 2008 |
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Keywords
- Microarray
- Prostate cancer
- TRAMP mice
- Tumor antigens
ASJC Scopus subject areas
- Oncology
- Urology
Cite this
Gene expression profile of mouse prostate tumors reveals dysregulations in major biological processes and identifies potential murine targets for preclinical development of human prostate cancer therapy. / Haram, Kerstyn M.; Peltier, Heidi J.; Lu, Bin; Bhasin, Manoj; Otu, Hasan H.; Choy, Bob; Regan, Meredith; Libermann, Towia A.; Latham, Gary J.; Sanda, Martin G.; Arredouani, Mohamed S.
In: Prostate, Vol. 68, No. 14, 01.10.2008, p. 1517-1530.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gene expression profile of mouse prostate tumors reveals dysregulations in major biological processes and identifies potential murine targets for preclinical development of human prostate cancer therapy
AU - Haram, Kerstyn M.
AU - Peltier, Heidi J.
AU - Lu, Bin
AU - Bhasin, Manoj
AU - Otu, Hasan H.
AU - Choy, Bob
AU - Regan, Meredith
AU - Libermann, Towia A.
AU - Latham, Gary J.
AU - Sanda, Martin G.
AU - Arredouani, Mohamed S.
PY - 2008/10/1
Y1 - 2008/10/1
N2 - BACKGROUND. Translation of preclinical studies into effective human cancer therapy is hampered by the lack of defined molecular expression patterns in mouse models that correspond to the human counterpart. We sought to generate an open source TRAMP mouse microarray dataset and to use this array to identify differentially expressed genes from human prostate cancer (PCa) that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. METHODS. We performed microarrays on total RNA extracted and amplified from eight TRAMP tumors and nine normal prostates. A subset of differentially expressed genes was validated by QRT-PCR. Differentially expressed TRAMP genes were analyzed for concordant expression in publicly available human prostate array datasets and a subset of resulting genes was analyzed by QRT-PCR. RESULTS. Cross-referencing differentially expressed TRAMP genes to public human prostate array datasets revealed 66 genes with concordant expression in mouse and human PCa; 56 between metastases and normal and 10 between primary tumor and normal tissues. Of these 10 genes, two, Sox4 and Tubb2a, were validated by QRT-PCR. Our analysis also revealed various dysregulations in major biologic pathways in the TRAMP prostates. CONCLUSIONS. We report a TRAMP microarray dataset of which a gene subset was validated by QRT-PCR with expression patterns consistent with previous gene-specific TRAMP studies. Concordance analysis between TRAMP and human PCa associated genes supports the utility of the model and suggests several novel molecular targets for preclinical therapy.
AB - BACKGROUND. Translation of preclinical studies into effective human cancer therapy is hampered by the lack of defined molecular expression patterns in mouse models that correspond to the human counterpart. We sought to generate an open source TRAMP mouse microarray dataset and to use this array to identify differentially expressed genes from human prostate cancer (PCa) that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. METHODS. We performed microarrays on total RNA extracted and amplified from eight TRAMP tumors and nine normal prostates. A subset of differentially expressed genes was validated by QRT-PCR. Differentially expressed TRAMP genes were analyzed for concordant expression in publicly available human prostate array datasets and a subset of resulting genes was analyzed by QRT-PCR. RESULTS. Cross-referencing differentially expressed TRAMP genes to public human prostate array datasets revealed 66 genes with concordant expression in mouse and human PCa; 56 between metastases and normal and 10 between primary tumor and normal tissues. Of these 10 genes, two, Sox4 and Tubb2a, were validated by QRT-PCR. Our analysis also revealed various dysregulations in major biologic pathways in the TRAMP prostates. CONCLUSIONS. We report a TRAMP microarray dataset of which a gene subset was validated by QRT-PCR with expression patterns consistent with previous gene-specific TRAMP studies. Concordance analysis between TRAMP and human PCa associated genes supports the utility of the model and suggests several novel molecular targets for preclinical therapy.
KW - Microarray
KW - Prostate cancer
KW - TRAMP mice
KW - Tumor antigens
UR - http://www.scopus.com/inward/record.url?scp=51649111988&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51649111988&partnerID=8YFLogxK
U2 - 10.1002/pros.20803
DO - 10.1002/pros.20803
M3 - Article
C2 - 18668517
AN - SCOPUS:51649111988
VL - 68
SP - 1517
EP - 1530
JO - Prostate
JF - Prostate
SN - 0270-4137
IS - 14
ER -