期刊
CANCER RESEARCH
卷 67, 期 19, 页码 9089-9096出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-07-2887
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资金
- NCI NIH HHS [U01-CA84294, CA115717, CA076501] Funding Source: Medline
- NHLBI NIH HHS [T32 HL07382-30] Funding Source: Medline
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 Runx-1. We propose that exposure to reduced androgens may promote prostate tumorigenesis by selecting for molecular events that promote more aggressive, hormone-refractory tumors.
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