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Publication : Emergence of androgen independence at early stages of prostate cancer progression in Nkx3.1; Pten mice.

First Author  Gao H Year  2006
Journal  Cancer Res Volume  66
Issue  16 Pages  7929-33
PubMed ID  16912166 Mgi Jnum  J:112106
Mgi Id  MGI:3655545 Doi  10.1158/0008-5472.CAN-06-1637
Citation  Gao H, et al. (2006) Emergence of androgen independence at early stages of prostate cancer progression in nkx3.1; pten mice. Cancer Res 66(16):7929-33
abstractText  Although androgen deprivation therapy is a widely used treatment for patients with advanced prostate cancer, it ultimately results in the emergence of a hormone-refractory disease that is invariably fatal. To provide insights into the genesis of this disease, we have employed an in vivo model to investigate how and when prostate epithelial cells can acquire the ability to survive and proliferate in the absence of androgens. In particular, we have been studying the evolution of androgen independence in Nkx3.1; Pten mutant mice, which develop prostatic intraepithelial neoplasia and adenocarcinoma as a consequence of aging, as well as androgen-independent phenotypes following castration. We now find that the prostate epithelial cells from these Nkx3.1; Pten mutant mice are capable of surviving and proliferating in the absence of androgens and that they develop androgen-independent phenotypes well before they display overt prostatic intraepithelial neoplasia or cancer phenotypes. Our findings in this mouse model show that acquisition of androgen independence can be uncoupled from overt cancer progression and raise the possibility that hormone-refractory disease can arise at early stages of prostate carcinogenesis. (Cancer Res 2006; 66(16): 7929-33).
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