Overexpression, amplification, and androgen regulation of TPD52 in prostate cancer.
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.
Rubin
Mark A
MA
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. marubin@partners.org
Varambally
Sooryanarayana
S
Beroukhim
Rameen
R
Tomlins
Scott A
SA
Rhodes
Daniel R
DR
Paris
Pamela L
PL
Hofer
Matthias D
MD
Storz-Schweizer
Martina
M
Kuefer
Rainer
R
Fletcher
Jonathan A
JA
Hsi
Bae-Li
BL
Byrne
Jennifier A
JA
Pienta
Kenneth J
KJ
Collins
Colin
C
Sellers
William R
WR
Chinnaiyan
Arul M
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000502:physiology*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*
D000728:Androgens; D009363:Neoplasm Proteins; C114751:TPD52 protein, human