Human prostate cancer xenografts in lit/lit mice exhibit reduced growth and androgen-independent progression

Kiyoshi Takahara, Howard Tearle, Mazyar Ghaffari, Martin E. Gleave, Michael Pollak, Michael E. Cox

研究成果: Article

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Background The growth hormone/insulin-like growth factor I (GH/IGF-I) axis has been linked to prostate cancer (PCa) risk. Although previous studies indicate that human breast cancers and a murine PCa model develop more slowly in murine hosts homozygous for a missense mutation in the GH-releasing hormone receptor (lit/lit) whose "little" dwarfed phenotype is caused by suppressed GH and IGF-I production, the role of these two hormones remains controversial. Methods To assess how the GH/IGF-I axis influences androgen-responsive, castration-resistant (CR), and androgen-independent (AI) growth of human PCa, we compared xenograft growth of the androgen-responsive human PCa cells, LNCaP, and AI human PCa cells, PC3, in intact and castrate Nod/SCID lit/lit and lit/+ mice, and in vitro growth of these cell lines in lit/lit and lit/+ serum-containing media supplemented with GH or IGF-I. Results Tumor growth and PSA accumulation rates were suppressed in LNCaP tumor-bearing lit/lit mice pre- and post-castration. Growth of PC3 xenografts in lit/lit mice was also suppressed. In vitro proliferation of LNCaP and PC3 cells cultured in media containing lit/lit mouse serum was decreased as compared to growth in media containing lit/+ serum. Suppressed growth in lit/lit serum could be restored by the addition of IGF-I, and to a lesser extent, GH. Differences in growth correlated with differences in steady-state AKT and ERK1/2 activation. ConclusionS This study demonstrates that circulating GH and IGF-I can promote androgen-responsive growth, CR progression, and AI expansion of PTEN-deficient human PCa cell xenografts and indicates that IGF-I can promote PCa growth in a suppressed GH environment. Prostate 77:525-537, 2011.

元の言語English
ページ(範囲)525-537
ページ数13
ジャーナルProstate
71
発行部数5
DOI
出版物ステータスPublished - 01-04-2011

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

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