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Comprehensive analyses of prostate gene expression: Convergence of expressed sequence tag databases, transcript profiling and proteomics
Author(s) -
Nelson Peter S.,
Han David,
Rochon Yvan,
Corthals Garry L.,
Lin Biaoyang,
Monson Adam,
Nguyen Vilaska,
Franza B. Robert,
Plymate Stephen R.,
Aebersold Ruedi,
Hood Leroy
Publication year - 2000
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/(sici)1522-2683(20000501)21:9<1823::aid-elps1823>3.0.co;2-3
Subject(s) - prostate cancer , androgen receptor , biology , expressed sequence tag , dna microarray , transcriptome , proteome , gene expression profiling , proteomics , gene , gene expression , computational biology , microarray , androgen , cancer research , bioinformatics , genetics , cancer , endocrinology , hormone
Several methods have been developed for the comprehensive analysis of gene expression in complex biological systems. Generally these procedures assess either a portion of the cellular transcriptome or a portion of the cellular proteome. Each approach has distinct conceptual and methodological advantages and disadvantages. We have investigated the application of both methods to characterize the gene expression pathway mediated by androgens and the androgen receptor in prostate cancer cells. This pathway is of critical importance for the development and progression of prostate cancer. Of clinical importance, modulation of androgens remains the mainstay of treatment for patients with advanced disease. To facilitate global gene expression studies we have first sought to define the prostate transcriptome by assembling and annotating prostate‐derived expressed sequence tags (ESTs). A total of 55 000 prostate ESTs were assembled into a set of 15 953 clusters putatively representing 15 953 distinct transcripts. These clusters were used to construct cDNA microarrays suitable for examining the androgen‐response pathway at the level of transcription. The expression of 20 genes was found to be induced by androgens. This cohort included known androgen‐regulated genes such as prostate‐specific antigen (PSA) and several novel complementary DNAs (cDNAs). Protein expression profiles of androgen‐stimulated prostate cancer cells were generated by two‐dimensional electrophoresis (2‐DE). Mass spectrometric analysis of androgen‐regulated proteins in these cells identified the metastasis‐suppressor gene NDKA/nm23, a finding that may explain a marked reduction in metastatic potential when these cells express a functional androgen receptor pathway.

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