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Expression of the IGF axis is decreased in local prostate cancer but enhanced after benign prostate epithelial differentiation and TGF-β treatment.
Am J Pathol 2011; 179(6):2905-19AJ

Abstract

The insulin-like growth factor (IGF) axis is a molecular pathway intensively investigated in cancer research. Clinical trials targeting the IGF1 receptor (IGF1R) in different tumors, including prostate cancer, are under way. Although studies on the IGF axis in prostate cancer have already entered into clinical trials, the expression and functional role of the IGF axis in benign prostate and in prostate cancer needs to be better defined. We determined mRNA expression levels of the IGF axis in microdissected tissue specimens of local prostate cancer using quantitative PCR. All members of the IGF axis, including IGF1, IGF2, IGF binding proteins 1 through 6, and insulin receptor, were measured in both the stromal and epithelial compartments of the prostate. IGF1, IGF2, IGF1R, and insulin receptor were down-regulated in local prostate cancer tissue compared with matched benign tissue, suggesting that the IGF axis is not induced during prostate cancer development. Using a new prostate epithelial differentiation model, we demonstrate that the expression of the IGF axis is enhanced during normal prostate epithelial differentiation and regulated by tumor growth factor (TGF)-β. Our data reveal a functional role of the IGF axis in prostate differentiation, underscoring the importance of the IGF axis in normal development and emphasizing the importance of accurate target validation before moving to advanced clinical trials.

Authors+Show Affiliations

Division of Experimental Urology, Department of Urology, Innsbruck Medical University, Innsbruck, Austria. Petra.Massoner@i-med.ac.atNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21983635

Citation

Massoner, Petra, et al. "Expression of the IGF Axis Is Decreased in Local Prostate Cancer but Enhanced After Benign Prostate Epithelial Differentiation and TGF-β Treatment." The American Journal of Pathology, vol. 179, no. 6, 2011, pp. 2905-19.
Massoner P, Ladurner Rennau M, Heidegger I, et al. Expression of the IGF axis is decreased in local prostate cancer but enhanced after benign prostate epithelial differentiation and TGF-β treatment. Am J Pathol. 2011;179(6):2905-19.
Massoner, P., Ladurner Rennau, M., Heidegger, I., Kloss-Brandstätter, A., Summerer, M., Reichhart, E., ... Klocker, H. (2011). Expression of the IGF axis is decreased in local prostate cancer but enhanced after benign prostate epithelial differentiation and TGF-β treatment. The American Journal of Pathology, 179(6), pp. 2905-19. doi:10.1016/j.ajpath.2011.08.026.
Massoner P, et al. Expression of the IGF Axis Is Decreased in Local Prostate Cancer but Enhanced After Benign Prostate Epithelial Differentiation and TGF-β Treatment. Am J Pathol. 2011;179(6):2905-19. PubMed PMID: 21983635.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of the IGF axis is decreased in local prostate cancer but enhanced after benign prostate epithelial differentiation and TGF-β treatment. AU - Massoner,Petra, AU - Ladurner Rennau,Michael, AU - Heidegger,Isabel, AU - Kloss-Brandstätter,Anita, AU - Summerer,Monika, AU - Reichhart,Eva, AU - Schäfer,Georg, AU - Klocker,Helmut, Y1 - 2011/10/06/ PY - 2011/02/28/received PY - 2011/08/01/revised PY - 2011/08/24/accepted PY - 2011/10/11/entrez PY - 2011/10/11/pubmed PY - 2012/2/10/medline SP - 2905 EP - 19 JF - The American journal of pathology JO - Am. J. Pathol. VL - 179 IS - 6 N2 - The insulin-like growth factor (IGF) axis is a molecular pathway intensively investigated in cancer research. Clinical trials targeting the IGF1 receptor (IGF1R) in different tumors, including prostate cancer, are under way. Although studies on the IGF axis in prostate cancer have already entered into clinical trials, the expression and functional role of the IGF axis in benign prostate and in prostate cancer needs to be better defined. We determined mRNA expression levels of the IGF axis in microdissected tissue specimens of local prostate cancer using quantitative PCR. All members of the IGF axis, including IGF1, IGF2, IGF binding proteins 1 through 6, and insulin receptor, were measured in both the stromal and epithelial compartments of the prostate. IGF1, IGF2, IGF1R, and insulin receptor were down-regulated in local prostate cancer tissue compared with matched benign tissue, suggesting that the IGF axis is not induced during prostate cancer development. Using a new prostate epithelial differentiation model, we demonstrate that the expression of the IGF axis is enhanced during normal prostate epithelial differentiation and regulated by tumor growth factor (TGF)-β. Our data reveal a functional role of the IGF axis in prostate differentiation, underscoring the importance of the IGF axis in normal development and emphasizing the importance of accurate target validation before moving to advanced clinical trials. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/21983635/abstract/ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(11)00843-1 DB - PRIME DP - Unbound Medicine ER -