Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/48247
Title: SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer
Authors: Iglesias-Gato, Diego
Chuan, Yin Choy
Wikström, Pernilla
Augsten, Sandra
Jiang, Ning
Niu, Yuanjie
Seipel, Amanda
Danneman, Daniela
Vermeij, Marcel
Fernandez-Perez, Leandro 
Jenster, Guido
Egevad, Lars
Norstedt, Gunnar
Flores-Morales, Amilcar 
Keywords: Gene-Expression
Factor-I
Receptor Expression
Prolactin
Transducer, et al
Issue Date: 2014
Publisher: 0143-3334
Journal: Carcinogenesis 
Abstract: Anabolic signals such as androgens and the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis play an essential role in the normal development of the prostate but also in its malignant transformation. In this study, we investigated the role of suppressor of cytokine signaling 2 (SOCS2) as mediator of the cross talk between androgens and GH signals in the prostate and its potential role as tumor suppressor in prostate cancer (PCa). We observed that SOCS2 protein levels assayed by immunohistochemistry are elevated in hormone therapy-naive localized prostatic adenocarcinoma in comparison with benign tissue. In contrast, however, castration-resistant bone metastases exhibit reduced levels of SOCS2 in comparison with localized or hormone naive, untreated metastatic tumors. In PCa cells, SOCS2 expression is induced by androgens through a mechanism that requires signal transducer and activator of transcription 5 protein (STAT5) and androgen receptor-dependent transcription. Consequentially, SOCS2 inhibits GH activation of Janus kinase 2, Src and STAT5 as well as both cell invasion and cell proliferation in vitro. In vivo, SOCS2 limits proliferation and production of IGF-1 in the prostate in response to GH. Our results suggest that the use of GH-signaling inhibitors could be of value as a complementary treatment for castration-resistant PCa.Summary: Androgen induced SOCS2 ubiquitin ligase expression and inhibited GH signaling as well as cell proliferation and invasion in PCa, whereas reduced SOCS2 was present in castration-resistant cases. GH-signaling inhibitors might be a complementary therapeutic option for advanced PCa.
URI: http://hdl.handle.net/10553/48247
ISSN: 0143-3334
DOI: 10.1093/carcin/bgt304
Source: Carcinogenesis[ISSN 0143-3334],v. 35, p. 24-33
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