Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis.
BACKGROUND
Cancer patients produce autoantibodies to self-proteins called tumor-associated antigens (TAA). These autoantibodies represent potentially valuable tools for identifying novel biomarkers and therapeutic targets. This study was designed to identify TAA in prostate cancer (PCa).


METHODS
Serum autoantibodies to the survival protein lens epithelium-derived growth factor p75 (LEDGF/p75) were detected by immunofluorescence microscopy, ELISA, and immunoblotting. Expression of LEDGF/p75 in prostate cells and tumors was evaluated by immunoblotting or immunohistochemistry. Apoptotic cleavage of LEDGF/p75 was detected by immunoblotting.


RESULTS
Anti-LEDGF/p75 autoantibodies were detected by ELISA in 18.4% of PCa patients and 5.5% of matched controls (P < 0.001) but not in patients with benign prostatic hyperplasia (BPH). LEDGF/p75 expression was detected in 93% of prostate tumors but not in normal prostate. Strong expression of the protein was observed in 61% of prostate tumors. Moderate to high expression was also detected in BPH tissue. Cleavage of LEDGF/p75 was detected in apoptotic prostate cells.


CONCLUSIONS
The high expression of LEDGF/p75 in prostate tumors and BPH could be induced by inflammation and oxidative stress. LEDGF/p75 cleavage fragments generated during prostate tumor cell death might trigger autoantibodies under inflammatory conditions in certain patients.
Daniels
Tracy
T
Loma Linda University School of Medicine, Department of Biochemistry and Microbiology and Center for Molecular Biology and Gene Therapy, 11085 Campus Street, Loma Linda, CA 92350, USA.
Zhang
Jianying
J
Gutierrez
Israel
I
Elliot
Max L
ML
Yamada
Brian
B
Heeb
Mary Jo
MJ
Sheets
Shaun M
SM
Wu
Xiwei
X
Casiano
Carlos A
CA
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D018233:Rhabdomyosarcoma, Embryonal / Q000276:immunology
D000974:Antibodies, Antinuclear; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor