Abstract
Despite extensive research, the mechanisms of prostate carcinogenesis are not well understood. The slow progress in this area is due, at least in part, to lack of a suitable animal model for prostate carcinogenesis. We have developed an animal model, based on the existing sex hormone-induced prostate carcinogenesis in the Noble rat, by substantially increasing the dosage of testosterone while keeping the level of estrogen unchanged. Using the modified method of combination of testosterone and estradiol-17beta (T+E2), it has been shown in Noble rats that prostate carcinogenesis followed a multi-step process involving hyperplasia, dysplasia, and carcinoma. We have demonstrated the importance of TGF-alpha, TGF-beta1 and bFGF in the development of prostate carcinogenesis. This study also established the roles of VEGF and IGF-1, initially as paracrine factors in epithelial-stromal interactions during the process of carcinogenesis and subsequently switching over to an autocrine mode during the establishment of carcinoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / chemically induced
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Adenocarcinoma / chemistry
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Adenocarcinoma / pathology*
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Animals
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Drug Therapy, Combination
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Endothelial Growth Factors / analysis
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Estradiol / toxicity
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Fibroblast Growth Factor 2 / analysis
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Hyperplasia / chemically induced
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Hyperplasia / pathology
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Immunohistochemistry
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Lymphokines / analysis
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Male
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Precancerous Conditions / chemically induced
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Precancerous Conditions / pathology
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Prostate / anatomy & histology
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Prostate / drug effects
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Prostate / pathology*
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Prostatic Neoplasms / chemically induced
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Prostatic Neoplasms / chemistry
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Prostatic Neoplasms / pathology*
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Rats
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Rats, Inbred Strains
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Receptor Protein-Tyrosine Kinases / analysis
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Receptors, Growth Factor / analysis
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Receptors, Vascular Endothelial Growth Factor
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Testosterone / administration & dosage
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Testosterone / toxicity
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Transforming Growth Factor alpha / analysis
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Transforming Growth Factor beta / analysis
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Transforming Growth Factor beta1
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Endothelial Growth Factors
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Lymphokines
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Receptors, Growth Factor
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Tgfb1 protein, rat
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Transforming Growth Factor alpha
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Fibroblast Growth Factor 2
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Testosterone
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Estradiol
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Receptor Protein-Tyrosine Kinases
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Receptors, Vascular Endothelial Growth Factor