Faculty Collaboration Database

Decreased pigment epithelium-derived factor is associated with metastatic phenotype in human and rat prostate tumors. Cancer Res 2004 Aug 15;64(16):5664-71

Date

08/18/2004

Pubmed ID

15313905

DOI

10.1158/0008-5472.CAN-04-0835

Scopus ID

2-s2.0-4143122398 (requires institutional sign-in at Scopus site)   78 Citations

Abstract

Pigment epithelium-derived factor, a potent angiogenesis inhibitor in the eye, is also expressed in the prostate. Prostate size and angiogenesis is increased in pigment epithelium-derived factor knockout mice, and pigment epithelium-derived factor is down-regulated in some prostate cancers. To investigate whether pigment epithelium-derived factor expression correlates with tumor progression, we examined 5 Dunning rat prostate sublines with different growth rates, differentiation, androgen dependence, vascular density, and metastatic ability and 26 human prostate cancers of Gleason score 8-10 obtained from patients at transurethral resection selected to represent two groups, with and without metastases at diagnosis. By Western blot, real-time quantitative reverse transcription-PCR, and immunostaining, pigment epithelium-derived factor was detected in highly differentiated, nonmetastatic, androgen-sensitive Dunning tumors and in the anaplastic, androgen insensitive but nonmetastatic Dunning tumors. In contrast, the metastatic Dunning tumor sublines showed very low pigment epithelium-derived factor expression levels. In human cancer tissues, by immunohistochemistry and real-time quantitative reverse transcription-PCR, patients without metastases at diagnosis had higher tumor pigment epithelium-derived factor levels than tumors from patients with metastases at diagnosis. In both the rat model and in the human tumors, the proliferation index and vascular count, as determined by Ki-67 staining and endoglin and/or factor VIII-related antigen staining, inversely correlated with pigment epithelium-derived factor mRNA levels. These observations indicate that loss of pigment epithelium-derived factor expression could be associated with the progression toward a metastatic phenotype in prostate cancer.

Author List

Halin S, Wikström P, Rudolfsson SH, Stattin P, Doll JA, Crawford SE, Bergh A

Author

Jennifer A. Doll PhD Assistant Professor in the Biomedical Sciences department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Animals
Cell Differentiation
Cell Line, Tumor
Disease Progression
Eye Proteins
Humans
Male
Neoplasm Metastasis
Nerve Growth Factors
Prostatic Neoplasms
Protein Biosynthesis
Rats
Serpins