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Vascular endothelial growth factor and angiopoietin are required for prostate regeneration
Author(s) -
Wang Guimin,
Kovalenko Bruce,
Huang Yili,
Moscatelli David
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20534
Subject(s) - endocrinology , medicine , vascular endothelial growth factor , angiopoietin , androgen receptor , androgen , testosterone (patch) , prostate , angiogenesis , prostate cancer , biology , castration , growth factor , receptor , hormone , cancer , vegf receptors
BACKGROUND The regulation of the prostate size by androgens may be partly the result of androgen effects on the prostatic vasculature. We examined the effect of changes in androgen levels on the expression of a variety of angiogenic factors in the mouse prostate and determined if vascular endothelial growth factor (VEGF)‐A and the angiopoietins are involved in the vascular response to androgens. METHODS Expression of angiogenic factors in prostate was quantitated using real‐time PCR at different times after castration and after administration of testosterone to castrated mice. Angiopoietins were localized in prostate by immunohistochemistry and in situ hybridization. The roles of VEGF and the angiopoietins in regeneration of the prostate were examined in mice inoculated with cells expressing soluble VEGF receptor‐2 or soluble Tie‐2. RESULTS Castration resulted in a decrease in VEGF‐A, VEGF‐B, VEGF‐C, placenta growth factor, FGF‐2, and FGF‐8 expression after 1 day. In contrast, VEGF‐D mRNA levels increased. No changes in angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2), hepatocyte growth factor, VEGF receptor‐1, VEGF receptor‐2, or tie‐2 mRNA levels were observed. Administration of testosterone to castrated mice had the opposite effect on expression of these angiogenic factors. Ang‐2 was expressed predominately in prostate epithelial cells whereas Ang‐1 was expressed in epithelium and smooth muscle. Inoculation of mice with cells expressing soluble VEGF receptor‐2 or Tie‐2 blocked the increase in vascular density normally observed after administration of testosterone to castrated mice. The soluble receptors also blocked the increase in prostate weight and proliferation of prostatic epithelial cells. CONCLUSION VEGF‐A and angiopoietins are required for the vascular response to androgens and for the ability of the prostate to regenerate in response to androgens. Prostate 67: 485–499, 2007. © 2007 Wiley‐Liss, Inc.