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Human prostate cancer xenografts in lit/lit mice exhibit reduced growth and androgen‐independent progression
Author(s) -
Takahara Kiyoshi,
Tearle Howard,
Ghaffari Mazyar,
Gleave Martin E.,
Pollak Michael,
Cox Michael E.
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21268
Subject(s) - lncap , endocrinology , prostate cancer , medicine , androgen , androgen receptor , growth factor , biology , prostate , cancer research , cancer , hormone , receptor
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. © 2010 Wiley‐Liss, Inc.