Adenovirus-mediated PEDF expression inhibits prostate cancer cell growth and results in augmented expression of PAI-2.
PEDF is one of the most potent inhibitor of angiogenesis. Loss of PEDF was found in human prostate tumors and associated with the progression toward a metastatic phenotype. To test the therapeutic potential of PEDF, we constructed a replication-defective adenoviral vector capable of efficient transduction and expression of PEDF (Ad-PEDF) in PC-3 prostate carcinoma cells. As controls, we used adenoviruses expressing beta-galactosidase (Ad-LacZ). We showed that overexpression of PEDF inhibited proliferation of cells and augmented apoptosis in serum-starved cells, in comparison with Ad-LacZ. Furthermore, Ad-PEDF suppresses anchorage-independent growth cells in soft agar and tumor formation in athymic nude mice associated with decreased microvessel density. Microarray analysis showed that 56 out of 8464 genes were found to be upregulated and downregulated in the PC-3 infected with Ad-PEDF as compared with Ad-LacZ. The differentially expressed genes cover a broad range of functional activities including catalytic activity, protein binding, signal transduction activity and cell invasion. Among them, PAI-2 and DRHC were confirmed to be upregulated with real-time PCR and Western blot, suggesting a possible association with PEDF-induced signaling for cell motility and metastasis. These results can contribute to our understanding of the molecular mechanisms of treatment strategies of PEDF for prostate cancer.
Guan
Ming
M
Center of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Jiang
Haowen
H
Xu
Chong
C
Xu
Rong
R
Chen
Zhongqing
Z
Lu
Yuan
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002196:Capillaries / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D005136:Eye Proteins / Q000235:genetics*; D018014:Gene Transfer Techniques; D052138:Genes, Neoplasm; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009414:Nerve Growth Factors / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000628:therapy*; D015843:Serpins / Q000235:genetics*; D015854:Up-Regulation; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D017396:Plasminogen Activator Inhibitor 2; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor