Differential expression of TRAIL and its receptors in benign and malignant prostate tissues.
OBJECTIVE
Because TRAIL (tumor necrosis factor related apoptosis inducing ligand) selectively kills cancer cells without damaging normal cells, a gene therapy approach using TRAIL is feasible for treating patients with cancer. However, recent publications suggest that significant portions of human tumors appear to be TRAIL resistant. Furthermore, there is some controversy about whether TRAIL receptor composition influences TRAIL sensitivity in cancer cells. Our recent studies suggest that TRAIL receptor composition is the major modulator of TRAIL sensitivity, as demonstrated using prostate, breast and lung cancer cells. We investigated TRAIL and TRAIL receptor expression profiles during prostate carcinogenesis to evaluate their potential as biomarkers and predict the feasibility of a related gene therapy approach.


METHODS
Paraffin embedded prostate tissues of 44 patients with benign prostatic hyperplasia, 28 with organ confined prostate carcinoma and 26 with advanced prostate carcinoma were analyzed using immunohistochemical staining procedures.


RESULTS
Significant levels of TRAIL-R4 decoy receptor expression were detected in patients with benign prostatic hyperplasia, and organ confined and advanced prostate carcinoma. All TRAIL markers tested appear to be valuable markers for separating patients with benign prostatic hyperplasia from patients with organ confined prostate carcinoma or advanced prostate carcinoma.


CONCLUSIONS
Due to high TRAIL-R4 expression in all patient groups complementary gene therapy modalities might be needed to bypass potential TRAIL-R4 induced resistance.
Sanlioglu
Ahter Dilsad
AD
Human Gene Therapy Unit, Faculty of Medicine, Akdeniz University, Antalya, Turkey.
Koksal
Ismail Turker
IT
Ciftcioglu
Akif
A
Baykara
Mehmet
M
Luleci
Guven
G
Sanlioglu
Salih
S
D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand