1. Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice.
- Author
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Banach-Petrosky W, Jessen WJ, Ouyang X, Gao H, Rao J, Quinn J, Aronow BJ, and Abate-Shen C
- Subjects
- Androgens metabolism, Animals, Disease Progression, Male, Mice, Mice, Inbred C57BL, Neoplasms, Hormone-Dependent metabolism, Neoplasms, Hormone-Dependent pathology, Orchiectomy, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Testosterone Propionate pharmacology, Androgens deficiency, Homeodomain Proteins genetics, Neoplasms, Hormone-Dependent genetics, PTEN Phosphohydrolase genetics, Prostatic Neoplasms genetics, Transcription Factors genetics
- Abstract
In this report, we have investigated the relationship between androgen levels and prostate tumorigenesis in Nkx3.1; Pten mutant mice, a genetically engineered mouse model of human prostate cancer. By experimentally manipulating serum levels of testosterone in these mice for an extended period (i.e., 7 months), we have found that prolonged exposure of Nkx3.1; Pten mutant mice to androgen levels that are 10-fold lower than normal (the "Low-T" group) resulted in a marked acceleration of prostate tumorigenesis compared with those exposed to androgen levels within the reference range (the "Normal-T" group). We found that prostate tumors from the Low-T mutant mice share a similar gene expression profile as androgen-independent prostate tumors from these mutant mice, which includes the deregulated expression of several genes that are up-regulated in human hormone-refractory prostate cancer, such as Vav3 and Runx1. We propose that exposure to reduced androgens may promote prostate tumorigenesis by selecting for molecular events that promote more aggressive, hormone-refractory tumors.
- Published
- 2007
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