SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer
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SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer. / 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.
In: Carcinogenesis, Vol. 35, No. 1, 2014, p. 24-33.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2014
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
VL - 35
SP - 24
EP - 33
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 1
ER -
ID: 58827561