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Basic Research

The influence of growth hormone/insulin-like growth factor deficiency on prostatic dysplasia in pbARR2-Cre, PTEN knockout mice

Prostate Cancer and Prostatic Diseases volume 16, pages 239–247 (2013)Cite this article

Subjects

Abstract

Background:

Elevated insulin-like growth factor-I (IGF-I) serum levels and phosphatase and tensin homolog (PTEN) loss are prostate cancer (PCa) risk factors that enhance androgen-responsive and castration-resistant PCa xenografts growth.

Methods:

The impact of suppressed growth hormone (GH)/IGF-I levels on neoplastic initiation of PTEN-deficient prostate epithelia was assessed histologically and by epithelial-to-mesenchymal marker expression in Ghrhr D60G homozygous (lit/lit) and heterozygous (lit/+) pbARR2-Cre, PTEN(fl/fl) (PTEN−/−) mice. How suppressed GH/IGF-I levels impacted growth of PTEN−/− mouse-derived prostate cells (MPPK) was examined by growth and survival signaling of cells cultured in lit/+ or lit/lit serum.

Results:

Body weight, prostate weight and serum GH and IGF-I levels were reduced in lit/lit relative to lit/+ PTEN−/− littermates. While the anterior lobes of lit/+ PTEN−/− prostates consistently presented swollen, indicative of ductal blockage, the degree of prostatic dysplasia in 15- and 20-week-old lit/lit and lit/+ PTEN−/− mice was indistinguishable as measured by normalized prostatic weight, tissue histology, or probasin, PSP94, E-cadherin, N-cadherin and vimentin expression. However, growth and AKT activation of MPPK cells was decreased when cultured in lit/lit serum as compared with lit/+ serum and restored in lit/lit serum supplemented with IGF-I and, to a lesser extent, GH.

Conclusions:

These results suggest that initiation of prostate carcinogenesis by loss of PTEN is not influenced by germline variation of genes encoding signaling molecules in the GH/IGF-I axis, but suggests that these factors may affect the progression of dysplastic phenotype and supports previous studies, indicating that the GH/IGF milieu does impact the growth of PTEN-deficient dysplastic prostatic cells once transformed.

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Acknowledgements

We thank Virginia Yago, Darrell Trendall, Estelle Li and Mary Bowden for their excellent technical assistance. This work was supported by Terry Fox Program in Prostate Cancer Progression grant from the National Cancer Institute of Canada (no. 017007) and a CIHR Doctoral Fellowship award (to MG).

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Author notes

  1. K Takahara and N Ibuki: These authors contributed equally to this work.

Authors and Affiliations

  1. The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada

    K Takahara, N Ibuki, M Ghaffari, H Tearle, C J Ong, M E Gleave & M E Cox

  2. Department of Urology, Osaka Medical College, Osaka, Japan

    K Takahara & H Azuma

  3. Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    M Ghaffari

  4. Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada

    M E Gleave & M E Cox

  5. Department of Medicine and Oncology, McGill University, Montreal, Quebec, Canada

    M Pollak

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  1. K Takahara
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Correspondence to M E Cox.

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Takahara, K., Ibuki, N., Ghaffari, M. et al. The influence of growth hormone/insulin-like growth factor deficiency on prostatic dysplasia in pbARR2-Cre, PTEN knockout mice. Prostate Cancer Prostatic Dis 16, 239–247 (2013). https://doi.org/10.1038/pcan.2013.14

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