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

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

doi:10.1093/carcin/bgt304

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

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

The NNF Center for Protein Research

29 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Carcinogenesis
Vol/bind	35
Udgave nummer	1
Sider (fra-til)	24-33
ISSN	0143-3334
DOI	https://doi.org/10.1093/carcin/bgt304
Status	Udgivet - jan. 2014

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1093/carcin/bgt304

https://academic.oup.com/carcin/article-pdf/35/1/24/14132216/bgt304.pdf

Citationsformater

Iglesias Gato, D., Chuan, Y. C., Wikström, P., Augsten, S., Jiang, N., Niu, Y., Seipel, A., Danneman, D., Vermeij, M., Fernandez-Perez, L., Jenster, G., Egevad, L., Norstedt, G., & Flores Morales, A. (2014). SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer. Carcinogenesis, 35(1), 24-33. https://doi.org/10.1093/carcin/bgt304

@article{f0dbc12da90a46ef8062b965ae270a65,

title = "SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer",

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.",

author = "{Iglesias Gato}, Diego and Chuan, {Yin Choy} and Pernilla Wikstr{\"o}m and Sandra Augsten and Ning Jiang and Yuanjie Niu and Amanda Seipel and Daniela Danneman and Marcel Vermeij and Leandro Fernandez-Perez and Guido Jenster and Lars Egevad and Gunnar Norstedt and {Flores Morales}, Amilcar",

year = "2014",

month = jan,

doi = "10.1093/carcin/bgt304",

language = "English",

volume = "35",

pages = "24--33",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "1",

}

TY - JOUR

T1 - SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer

AU - Iglesias Gato, Diego

AU - Chuan, Yin Choy

AU - Wikström, Pernilla

AU - Augsten, Sandra

AU - Jiang, Ning

AU - Niu, Yuanjie

AU - Seipel, Amanda

AU - Danneman, Daniela

AU - Vermeij, Marcel

AU - Fernandez-Perez, Leandro

AU - Jenster, Guido

AU - Egevad, Lars

AU - Norstedt, Gunnar

AU - Flores Morales, Amilcar

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

U2 - 10.1093/carcin/bgt304

DO - 10.1093/carcin/bgt304

M3 - Journal article

C2 - 24031028

SN - 0143-3334

VL - 35

SP - 24

EP - 33

JO - Carcinogenesis

JF - Carcinogenesis

IS - 1

ER -

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

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater