Purine-rich element binding protein (PUR) alpha induces endoplasmic reticulum stress response, and cell differentiation pathways in prostate cancer cells.
BACKGROUND
Following androgen ablation treatment for advanced prostate cancer, almost all men relapse after a period of initial response to therapy, which eventually is life threatening. We have previously found that purine-rich element binding protein, PURalpha, was significantly repressed in androgen-independent prostate cancer cell lines in comparison to an androgen-dependent line. Moreover, over-expressing PURalpha in androgen-independent prostate cancer cells attenuated their cell proliferation. The aim of the studies described here was to uncover some of the mechanisms by which over-expression of PURalpha attenuates cell proliferation.


METHODS
A set of common genes induced by over-expressing PURalpha both in PC3 and LNCaP cells was analyzed by DNA microarray. The results were then validated utilizing quantitative reverse transcription-PCR. Using a 5.3-kb region of the PSA promoter containing androgen response elements, the participation of PURalpha in androgen regulated gene expression was determined.


RESULTS
Genes involved in stress response and cell differentiation were induced in cells over-expressing PURalpha. Some of the genes that are targets of androgen regulation are also induced. Most strikingly, ectopic expression of PURalpha induced transcriptional activity of the 5.3-kb PSA promoter containing androgen response elements, without androgen stimulation.


CONCLUSIONS
Based upon the consideration that some of the genes involved in cell stress and differentiation are also regulated by androgens our data suggest that PURalpha shares some common pathways regulated by the androgen receptor. These findings suggest that regulation of PURalpha expression in prostate cancer cells may serve as a therapeutic target for hormone refractory prostate cancer.
Inoue
Takahiro
T
James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, 600 North Wolfe St., Baltimore, MD 21287, USA.
Maeno
Atsushi
A
Talbot
Conover
C
Zeng
Yu
Y
Yeater
David B
DB
Leman
Eddy S
ES
Kulkarni
Prakash
P
Ogawa
Osamu
O
Getzenberg
Robert H
RH
D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D014183:Transplantation, Heterologous
D000906:Antibodies; D004268:DNA-Binding Proteins; C501130:PURA protein, human; D014157:Transcription Factors