The potential role of purine-rich element binding protein (PUR) alpha as a novel treatment target for hormone-refractory prostate cancer.
BACKGROUND
Hormonal therapy for advanced prostate cancer is typically effective at first, but almost all men suffer refractory disease which often is life threatening. The nuclear matrix comprises not only of the structural elements of the nucleus, but is associated with many components of the molecular machinery. Our aim is to find novel targets for the treatment of hormone-refractory prostate cancer (HRPC) by focusing on the composition of the nuclear matrix proteins (NMPs).


METHODS
LN96 cells were established at our Institution after long-term culturing of LNCaP cells under androgen deprived conditions. The composition of NMPs of LNCaP cells and LN96 cells were analyzed by two-dimensional (2D) electrophoresis and spots differentially expressed were investigated by mass spectrometry for identification. Among the spots identified, we analyzed the potential functional role of the identified proteins in prostate cancer cells by establishing stable overexpressed cells.


RESULTS
We found that purine-rich element binding protein (PUR)alpha was significantly repressed not only in NMPs but also in total protein and mRNA levels of LN96 cells in comparison to LNCaP cells under the same steroid deprived conditions. Moreover, PURalpha was decreased in its expression both at the protein and mRNA levels in the androgen-independent prostate cancer cell lines, PC3 and DU145 in comparison to LNCaP cells. Stably overexpressing PURalpha in PC3 and DU145 cells negatively regulates cell proliferation, resulting in decreases in PCNA expression.


CONCLUSIONS
Further dissection of the role of PURalpha in cell growth regulation may reveal a novel target for HRPC.
Inoue
Takahiro
T
James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Leman
Eddy S
ES
Yeater
David B
DB
Getzenberg
Robert H
RH
D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D008297:Male; D016296:Mutagenesis; D015530:Nuclear Matrix / Q000502:physiology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D011944:Receptors, Androgen / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D006728:Hormones; C501130:PURA protein, human; D011944:Receptors, Androgen; D014157:Transcription Factors