Overexpression, amplification, and androgen regulation of TPD52 in prostate cancer

Mark A. Rubin*, Sooryanarayana Varambally, Rameen Beroukhim, Scott A. Tomlins, Daniel R. Rhodes, Pamela L. Paris, Matthias D. Hofer, Martina Storz-Schweizer, Rainer Kuefer, Jonathan A. Fletcher, Bae Li Hsi, Jennifier A. Byrne, Kenneth J. Pienta, Colin Collins, William R. Sellers, Arul M. Chinnaiyan

*Corresponding author for this work

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

Gains in the long arm of chromosome 8 (8q) are believed to be associated with poor outcome and the development of hormone-refractory prostate cancer. Based on a meta-analysis of gene expression microarray data from multiple prostate cancer studies (D. R. Rhodes et al., Cancer Res 2002;62:4427-33), a candidate oncogene, Tumor Protein D52 (TPD52), was identified in the 8q21 amplicon. TPD52 is a coiled-coil motif-bearing protein, potentially involved in vesicle trafficking. Both mRNA and protein levels of TPD52 were highly elevated in prostate cancer tissues. Array comparative genomic hybridization and amplification analysis using single nucleotide polymorphism arrays demonstrated increased DNA copy number in the region encompassing TPD52. Fluorescence in situ hybridization on tissue microarrays confirmed TPD52 amplification in prostate cancer epithelia. Furthermore, our studies suggest that TPD52 protein levels may be regulated by androgens, consistent with the presence of androgen response elements in the upstream promoter of TPD52. In summary, these findings suggest that dysregulation of TPD52 by genomic amplification and androgen induction may play a role in prostate cancer progression.

Original languageEnglish (US)
Pages (from-to)3814-3822
Number of pages9
JournalCancer Research
Volume64
Issue number11
DOIs
StatePublished - Jun 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Rubin, M. A., Varambally, S., Beroukhim, R., Tomlins, S. A., Rhodes, D. R., Paris, P. L., Hofer, M. D., Storz-Schweizer, M., Kuefer, R., Fletcher, J. A., Hsi, B. L., Byrne, J. A., Pienta, K. J., Collins, C., Sellers, W. R., & Chinnaiyan, A. M. (2004). Overexpression, amplification, and androgen regulation of TPD52 in prostate cancer. Cancer Research, 64(11), 3814-3822. https://doi.org/10.1158/0008-5472.CAN-03-3881