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Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue
I B Joseph1, J B Nelson, S R Denmeade
1Johns Hopkins Oncology Center, Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Summary
Androgens control prostate cancer growth by regulating vascular endothelial growth factor (VEGF). Androgen ablation reduces VEGF, inhibiting tumor growth and angiogenesis, while androgen replacement increases VEGF levels.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Androgen ablation inhibits prostate cancer xenograft growth through apoptosis and reduced angiogenesis.
- Tumor angiogenesis is linked to vascular endothelial growth factor (VEGF) levels.
Purpose of the Study:
- To determine if androgens consistently regulate angiogenesis by controlling VEGF levels in various prostate cancer models.
- To investigate androgen regulation of VEGF in normal prostatic tissue.
- To assess if androgens directly stimulate VEGF secretion.
Main Methods:
- Tested androgen-sensitive human (LnCaP) and rodent (Dunning G and H) prostate cancer sublines.
- Performed castration and androgen replacement in male rats to measure ventral prostate VEGF.
- Assayed androgen-induced VEGF level changes in LnCaP cells in vitro.
Main Results:
- Androgen ablation decreased growth and reduced VEGF levels by >60% in tested sublines.
- Castration significantly decreased ventral prostate VEGF; androgen replacement increased it 8-fold.
- Androgens directly stimulated VEGF secretion in LnCaP cells.
- Elevated VEGF in prostatic fluid suggests a role in benign prostatic hyperplasia and prostate cancer progression.
Conclusions:
- Androgens directly stimulate VEGF production, influencing angiogenesis.
- Androgen sensitivity in prostate tissue growth involves VEGF regulation.
- Targeting the androgen-VEGF pathway may offer therapeutic strategies for prostate conditions.