Castration triggers growth of previously static androgen‐independent lesions in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model

Mac A. Johnson; Philip Iversen; Phillip Schwier; Angela L. Corn; George Sandusky; Jeremy Graff; Blake Lee Neubauer

doi:10.1002/pros.20148

journal article Jul 23, 2004

Castration triggers growth of previously static androgen‐independent lesions in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model

Mac A. Johnson Philip Iversen Phillip Schwier Angela L. Corn George Sandusky

Jeremy Graff Blake Lee Neubauer

The Prostate Vol. 62 No. 4 pp. 322-338 · Wiley

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Abstract

AbstractBackgroundAndrogen‐deprivation remains the standard of care for metastatic prostate cancer, yet its total impact on the course of disease is incompletely established.MethodsWe have examined the long‐term effects of castration upon the progression of established cancer in the TRAMP transgenic mouse model of prostate cancer. Mice castrated at 15‐weeks of age, as well as intact littermates, were followed until spontaneous death from cancer.ResultsStatistical analyses of age‐at‐death versus primary tumor mass revealed that mice segregate into two categories of response to androgen‐deprivation. In Category One, the act of castration paradoxically triggers the growth of microscopic androgen‐independent lesions, as evidenced by a statistical synchronization of primary tumor growth. Delaying castration until 20‐weeks of age delays the synchronized growth of these tumors, as well as the deaths of the host mice. In Category Two, castration eliminates or substantially delays primary tumor growth, but fails to eliminate metastases. so that castration is found to impart no long‐term survival advantage.ConclusionsWe propose a two‐step model for the alteration of androgen signaling in prostate cancer capable of explaining the above paradoxical results, which is based upon the dualistic role of androgens as both survival and differentiation factors. This model makes specific predictions for clinical intervention that are discussed in light of published studies. © 2004 Wiley‐Liss, Inc.

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Published: Jul 23, 2004
Vol/Issue: 62(4)
Pages: 322-338
License: View

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Cite This Article

Mac A. Johnson, Philip Iversen, Phillip Schwier, et al. (2004). Castration triggers growth of previously static androgen‐independent lesions in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. The Prostate, 62(4), 322-338. https://doi.org/10.1002/pros.20148

Castration triggers growth of previously static androgen‐independent lesions in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model

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