Proteomic profiling of the effect of prostate-specific antigen on prostate cancer cells.
BACKGROUND
Prostate-specific antigen (PSA) is a well-known biomarker for diagnosis and management of prostate cancer. PSA has been shown to have anti-angiogenic activity. We used the emerging proteomic research technology to identify proteins in prostate cancer cells whose expression is regulated by enzymatically active PSA.


METHODS
Differentially expressed proteins in PC-3M cells treated with PSA were analyzed by 2D-DIGE analysis and identified by HPLC-MS/MS and SEQUEST data mining. Biological network analysis was carried out using MetaCore integrated software designed for functional analysis of experimental data. Gene expression data for several regulated proteins were confirmed by real-time, quantitative PCR.


RESULTS
A total of 41 proteins were significantly (P < 0.05) changed in abundance in PC-3M cells in response to PSA treatment. Proteins from 26 gel-spots were identified. Many of the down-regulated proteins including N8 gene product long isoform, laminin receptor, vimentin, DJ-1 and Hsp60 are known to be involved in tumor progression.


CONCLUSIONS
The relevance of the level of PSA in prostate tissue microenvironment and its relation to tumor progression has not been elucidated. PSA has been shown to down-regulate several proteins that are known to have involvement in tumor progression. This suggests that normal physiological levels of PSA in prostate tissue microenvironment may be promoting non-angiogenic environment and its down-regulation may promote tumor growth.
Bindukumar
B
B
Department of Molecular & Cellular Biology, Roswell Park Cancer Research Institute, Buffalo, New York 14263, USA.
Schwartz
Stanley
S
Aalinkeel
Ravikumar
R
Mahajan
Supriya
S
Lieberman
Alicia
A
Chadha
Kailash
K
D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D005456:Fluorescent Dyes / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005456:Fluorescent Dyes; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D017430:Prostate-Specific Antigen