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

Kerstyn M. Haram, Heidi J. Peltier, Bin Lu, Manoj Bhasin, Hasan H. Otu, Bob Choy, Meredith Regan, Towia A. Libermann, Gary J. Latham, Martin G. Sanda, Mohamed S. Arredouani

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1517-1530
Number of pages14
JournalProstate
Volume68
Issue number14
DOIs
StatePublished - Oct 1 2008

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Biological Phenomena
Human Development
Transcriptome
Prostate
Prostatic Neoplasms
Genes
Neoplasms
Polymerase Chain Reaction
Therapeutics
Neoplasm Genes
RNA
Neoplasm Metastasis

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 journalArticle

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. / 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. In: Prostate. 2008 ; Vol. 68, No. 14. pp. 1517-1530.
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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.",
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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.

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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.

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KW - Prostate cancer

KW - TRAMP mice

KW - Tumor antigens

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