SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer.

Abstract

UNLABELLED:

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.

• Authors: Diego Iglesias-Gato, Yin-Choy Chuan, Pernilla Wikström, Sandra Augsten, Ning Jiang, Yuanjie Niu, Amanda Seipel, Daniela Danneman, Marcel Vermeij, Leandro Fernandez-Perez, Guido Jenster, Lars Egevad, Gunnar Norstedt, Amilcar Flores-Morales
• Journal: Carcinogenesis (Carcinogenesis) Vol. 35 Issue 1 Pg. 24-33 (Jan 2014) ISSN: 1460-2180 [Electronic] England
• PMID: 24031028 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• Receptors, Androgen
• SOCS2 protein, human
• STAT5 Transcription Factor
• Suppressor of Cytokine Signaling Proteins
• Human Growth Hormone
• Metribolone
• Insulin-Like Growth Factor I

Topics

• Adenocarcinoma (metabolism, pathology)
• Aged
• Androgens (metabolism)
• Animals
• Cell Line, Tumor (drug effects)
• Cell Proliferation (drug effects)
• Human Growth Hormone (metabolism, pharmacology)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Male
• Metribolone (pharmacology)
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Middle Aged
• Predictive Value of Tests
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Prostatic Neoplasms, Castration-Resistant (metabolism)
• Receptors, Androgen (metabolism)
• STAT5 Transcription Factor (metabolism)
• Signal Transduction
• Suppressor of Cytokine Signaling Proteins (analysis, genetics, metabolism)