Indeed, the conclusion that androgen deprivation therapy encourages prostate cancer cells to accelerate tumor development may be correlative. However, strong correlation often warrants further investigation to determine causation. That’s why I indicated that more research needed to be done. Nevertheless, the results of the final experiment in the study in mouse xenografts (transplanted prostate cancer cells expressing Nestin) are far from correlative and clearly demonstrate that Nestin expression is sufficient to increase metastasis.

I mentioned the second study (engineered mouse model) to show that an unrelated investigation reached a similar conclusion i.e. prolonged exposure to low levels of androgen can promote, rather than prevent, prostate carcinogenesis. In that study, all the mice with normal levels of testosterone (n=15) and all of the mice in the mock group (n=6) displayed low- and high-grade PIN but not cancer. In comparison, over 70% of mice with low levels of testosterone displayed high-grade PIN with invasive carcinoma. Thus, low levels of testosterone are sufficient to promote an accelerated phenotype.

You raise a valid point regarding the possibility of Nestin being regulated by androgen. I should have indicated that many studies have been performed to identify androgen-regulated genes (ARGs) over the last decade and Nestin has never been identified:

Xu et al. Quantitative expression profile of androgen-regulated genes in prostate cancer cells and identification of prostate-specific genes. Int J Cancer. 2001 May 1;92(3):322-8.
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DePrimo et al. Transcriptional programs activated by exposure of human prostate cancer cells to androgen. Genome Biol. 2002 Jun 14;3(7):RESEARCH0032. Epub 2002 Jun 14.
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Nelson et al. The program of androgen-responsive genes in neoplastic prostate epithelium. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11890-5. Epub 2002 Aug 16.
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Segawa et al. Androgen-induced expression of endoplasmic reticulum (ER) stress response genes in prostate cancer cells. Oncogene. 2002 Dec 12;21(57):8749-58.
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Velasco et al. Identification and validation of novel androgen-regulated genes in prostate cancer. Endocrinology. 2004 Aug;145(8):3913-24. Epub 2004 May 6.
View abstract

… if you make it harder but not impossible for a somewhat heterogeneous group of cells to proliferate, the more aggressive ones will eventually dominate …

Absolutely. The authors of the first study speculate that Nestin expression may provide a selective advantage and the authors of the second study reach a similar conclusion – low levels of testosterone may provide a selective advantage for the outgrowth of androgen-independent prostate cancer cells.

Although drawing the conclusions you’re getting to is coming a little close to making a causation out of a correlation, and other possibilities involving Nestin and androgens being co-regulated are possible, I think the conclusions do make some sense. In general, if you make it harder but not impossible for a somewhat heterogeneous group of cells to proliferate, the more aggressive ones will eventually dominate, right? The analogous situation that comes to my mind is hypoxia and HIF-1 stimulating angiogenesis.