title: Sex hormone-induced prostatic carcinogenesis in the noble rat: the role of insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in the development of prostate cancer.
abstract: BACKGROUND
  Despite extensive effort, the mechanisms of prostate carcinogenesis are still unknown. We report on a modified method which enabled us to induce a high incidence of prostate carcinogenesis in the Noble rat and examined the role of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) and their receptors during sex hormone-induced prostate carcinogenesis.
  
  
  METHODS
  Noble rats were implanted subcutaneously with a combination of testosterone and estradiol capsules for up to 12 months. Animals were sacrificed starting at 2 months after implantation, and the prostate gland was removed for histopathological and immunohistochemical studies.
  
  
  RESULTS
  The results showed that hyperplasia/dysplasia was detected as early as 2 months after treatment, while carcinoma in situ was induced in 4 months and adenocarcinoma in 7 months. Our data suggest that IGF-1, produced by stromal cells in hyperplasia, exerted its effects, through a paracrine mode, on epithelial cells which were IGF-1 receptor (IGF-1R)-positive. The production of IGF-1 appeared to switch to epithelial cells in adenocarcinoma, through which it regulated tumor cell growth via autocrine mode by binding to IGF-1R of carcinoma cells. On the other hand, VEGF was overexpressed in hyperplastic/dysplastic and carcinoma cells, while VEGF-R was detected in endothelial cells. The results suggest that overexpression of VEGF in deranged epithelia and arterial muscle cells may exert its influence on stromal angiogenesis and abnormal growth of prostate gland.
  
  
  CONCLUSIONS
  A modified Noble rat model with a high incidence of prostate carcinogenesis has been developed. Using this model, we have further established that IGF-1 and VEGF may be the critical regulators in mediating epithelial-stromal interactions in sex hormone-induced prostate carcinogenesis.
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Wang
authors.forename: Y C
authors.initials: YC
authors.lastname: Wong
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000473:pathology; D000818:Animals; D002278:Carcinoma in Situ / Q000209:etiology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000502:physiology*; D008222:Lymphokines / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D011470:Prostatic Hyperplasia / Q000209:etiology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1