Abstract | BACKGROUND: 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.
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Authors | Kiyoshi Takahara, Howard Tearle, Mazyar Ghaffari, Martin E Gleave, Michael Pollak, Michael E Cox |
Journal | The Prostate
(Prostate)
Vol. 71
Issue 5
Pg. 525-37
(Apr 2011)
ISSN: 1097-0045 [Electronic] United States |
PMID | 20878948
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 Wiley-Liss, Inc. |
Chemical References |
- Androgens
- Human Growth Hormone
- Insulin-Like Growth Factor I
- Oncogene Protein v-akt
- Extracellular Signal-Regulated MAP Kinases
- Prostate-Specific Antigen
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Topics |
- Androgens
(physiology)
- Animals
- Blotting, Western
- Body Weight
(physiology)
- Cell Line, Tumor
- Cell Proliferation
- Disease Models, Animal
- Enzyme Activation
(physiology)
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Human Growth Hormone
(blood, metabolism)
- Humans
- Insulin-Like Growth Factor I
(analysis, metabolism)
- Male
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Neoplasm Transplantation
- Neoplasms, Hormone-Dependent
(enzymology, metabolism, pathology)
- Oncogene Protein v-akt
(metabolism)
- Prostate-Specific Antigen
(blood, metabolism)
- Prostatic Neoplasms
(enzymology, metabolism, pathology)
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