Androgens modulate the balance between VEGF and angiopoietin expression in prostate epithelial and smooth muscle cells.
BACKGROUND
The vasculature of the prostate responds to androgens. Androgens most likely affect the vasculature indirectly by modulating the expression of angiogenic factors in the cells of the prostate. Most studies to date have examined the production of angiogenic factors by the prostate luminal epithelium. Here we examine the effects of androgen on production of three angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin-1, and angiopoietin-2, by the three major cell types in the prostate.


METHODS
The ability of androgen to modulate VEGF, angiopoietin-1, and angiopoietin-2 production in cultured mouse prostate luminal epithelial, basal epithelial, and smooth muscle cells (SMCs) was assessed by Western blot and RT-PCR.


RESULTS
The production of VEGF was modulated by androgens in both luminal epithelial and prostate SMCs but not in basal epithelial cells. However, in prostate luminal epithelial cell cultures, VEGF was predominately secreted apically, suggesting that in vivo most of the epithelium-derived VEGF is unavailable to the underlying blood vessels. In addition, prostate luminal epithelial cells produced angiopoietin-2, an angiogenesis inhibitor. In contrast, prostate SMCs produced angiopoietin-1, a positive modulator of angiogenesis. Synthesis of the angiopoietins did not respond to androgen treatment.


CONCLUSIONS
Prostate smooth muscle may play an important role in regulating vascular responses to androgen.
Richard
Christian
C
Department of Cell Biology and the Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
Kim
Gilbert
G
Koikawa
Yasuhiro
Y
Salm
Sarah N
SN
Tsujimura
Akira
A
Wilson
E Lynette
EL
Moscatelli
David
D
D000728:Androgens / Q000494:pharmacology*; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D018929:Cell Culture Techniques; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000502:physiology; D005786:Gene Expression Regulation; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D009130:Muscle, Smooth / Q000502:physiology; D009389:Neovascularization, Pathologic; D011467:Prostate / Q000502:physiology*; D014176:Protein Biosynthesis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000728:Androgens; D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008562:Membrane Glycoproteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors