LNCaP prostate cancer cells with autocrine interleukin-6 expression are resistant to IL-6-induced neuroendocrine differentiation due to increased expression of suppressors of cytokine signaling

Dongxia Ge, Allen C Gao, Qiuyang Zhang, Sen Liu, Yun Xue, Zongbing You

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

BACKGROUND Neuroendocrine differentiation (NED) is one of the mechanisms underlying development of castration-resistant prostate cancer (CRPC). In this study, we investigated IL-6-induced NED in two LNCaP sublines. METHODS LNCaP-S17, an LNCaP subline that secretes IL-6, and LNCaP-C3, a control subline that does not express IL-6, were analyzed for IL-6-induced NED, activation of JAK2 and STAT3 pathways, and expression of IL-6/IL-6R signaling proteins and downstream target genes. RESULTS IL-6 did not induce NED in LNCaP-S17 cells, even though IL-6 induced NED in LNCaP-C3 cells. IL-6 activated JAK2 and STAT3 pathways in LNCaP-C3 cells but not in LNCaP-S17 cells. IL-6 did not activate ERK1/2, AKT, or NF-κB pathways in either cell line. Both LNCaP-C3 and LNCaP-S17 cell lines expressed IL-6R, gp130, and TYK2 at almost the same levels and did not express JAK1 or JAK3. The basal level of JAK2 expression was slightly higher in LNCaP-C3 cells than in LNCaP-S17 cells. Two suppressors of cytokine signaling, SOCS7 and cytokine-inducible SH2 protein (CIS), were expressed constitutively at higher levels in LNCaP-S17 cells than in LNCaP-C3 cells, while SOCS1 to SOCS6 were expressed at approximately the same levels. Using siRNA to knockdown SOCS7 and CIS expression in LNCaP-S17 cells led to increased phosphorylation of STAT3 upon IL-6 stimulation. CONCLUSIONS LNCaP-S17 cells are resistant to exogenous IL-6-induced NED due to increased levels of CIS/SOCS7 that block activation of JAK2-STAT3 pathways.

Original languageEnglish (US)
Pages (from-to)1306-1316
Number of pages11
JournalProstate
Volume72
Issue number12
DOIs
StatePublished - Sep 1 2012

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Interleukin-6
Prostatic Neoplasms
Cytokines
Proteins
Cell Line
Castration
Small Interfering RNA
Phosphorylation

Keywords

  • IL-6
  • neuroendocrine
  • prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

LNCaP prostate cancer cells with autocrine interleukin-6 expression are resistant to IL-6-induced neuroendocrine differentiation due to increased expression of suppressors of cytokine signaling. / Ge, Dongxia; Gao, Allen C; Zhang, Qiuyang; Liu, Sen; Xue, Yun; You, Zongbing.

In: Prostate, Vol. 72, No. 12, 01.09.2012, p. 1306-1316.

Research output: Contribution to journalArticle

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title = "LNCaP prostate cancer cells with autocrine interleukin-6 expression are resistant to IL-6-induced neuroendocrine differentiation due to increased expression of suppressors of cytokine signaling",
abstract = "BACKGROUND Neuroendocrine differentiation (NED) is one of the mechanisms underlying development of castration-resistant prostate cancer (CRPC). In this study, we investigated IL-6-induced NED in two LNCaP sublines. METHODS LNCaP-S17, an LNCaP subline that secretes IL-6, and LNCaP-C3, a control subline that does not express IL-6, were analyzed for IL-6-induced NED, activation of JAK2 and STAT3 pathways, and expression of IL-6/IL-6R signaling proteins and downstream target genes. RESULTS IL-6 did not induce NED in LNCaP-S17 cells, even though IL-6 induced NED in LNCaP-C3 cells. IL-6 activated JAK2 and STAT3 pathways in LNCaP-C3 cells but not in LNCaP-S17 cells. IL-6 did not activate ERK1/2, AKT, or NF-κB pathways in either cell line. Both LNCaP-C3 and LNCaP-S17 cell lines expressed IL-6R, gp130, and TYK2 at almost the same levels and did not express JAK1 or JAK3. The basal level of JAK2 expression was slightly higher in LNCaP-C3 cells than in LNCaP-S17 cells. Two suppressors of cytokine signaling, SOCS7 and cytokine-inducible SH2 protein (CIS), were expressed constitutively at higher levels in LNCaP-S17 cells than in LNCaP-C3 cells, while SOCS1 to SOCS6 were expressed at approximately the same levels. Using siRNA to knockdown SOCS7 and CIS expression in LNCaP-S17 cells led to increased phosphorylation of STAT3 upon IL-6 stimulation. CONCLUSIONS LNCaP-S17 cells are resistant to exogenous IL-6-induced NED due to increased levels of CIS/SOCS7 that block activation of JAK2-STAT3 pathways.",
keywords = "IL-6, neuroendocrine, prostate cancer",
author = "Dongxia Ge and Gao, {Allen C} and Qiuyang Zhang and Sen Liu and Yun Xue and Zongbing You",
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TY - JOUR

T1 - LNCaP prostate cancer cells with autocrine interleukin-6 expression are resistant to IL-6-induced neuroendocrine differentiation due to increased expression of suppressors of cytokine signaling

AU - Ge, Dongxia

AU - Gao, Allen C

AU - Zhang, Qiuyang

AU - Liu, Sen

AU - Xue, Yun

AU - You, Zongbing

PY - 2012/9/1

Y1 - 2012/9/1

N2 - BACKGROUND Neuroendocrine differentiation (NED) is one of the mechanisms underlying development of castration-resistant prostate cancer (CRPC). In this study, we investigated IL-6-induced NED in two LNCaP sublines. METHODS LNCaP-S17, an LNCaP subline that secretes IL-6, and LNCaP-C3, a control subline that does not express IL-6, were analyzed for IL-6-induced NED, activation of JAK2 and STAT3 pathways, and expression of IL-6/IL-6R signaling proteins and downstream target genes. RESULTS IL-6 did not induce NED in LNCaP-S17 cells, even though IL-6 induced NED in LNCaP-C3 cells. IL-6 activated JAK2 and STAT3 pathways in LNCaP-C3 cells but not in LNCaP-S17 cells. IL-6 did not activate ERK1/2, AKT, or NF-κB pathways in either cell line. Both LNCaP-C3 and LNCaP-S17 cell lines expressed IL-6R, gp130, and TYK2 at almost the same levels and did not express JAK1 or JAK3. The basal level of JAK2 expression was slightly higher in LNCaP-C3 cells than in LNCaP-S17 cells. Two suppressors of cytokine signaling, SOCS7 and cytokine-inducible SH2 protein (CIS), were expressed constitutively at higher levels in LNCaP-S17 cells than in LNCaP-C3 cells, while SOCS1 to SOCS6 were expressed at approximately the same levels. Using siRNA to knockdown SOCS7 and CIS expression in LNCaP-S17 cells led to increased phosphorylation of STAT3 upon IL-6 stimulation. CONCLUSIONS LNCaP-S17 cells are resistant to exogenous IL-6-induced NED due to increased levels of CIS/SOCS7 that block activation of JAK2-STAT3 pathways.

AB - BACKGROUND Neuroendocrine differentiation (NED) is one of the mechanisms underlying development of castration-resistant prostate cancer (CRPC). In this study, we investigated IL-6-induced NED in two LNCaP sublines. METHODS LNCaP-S17, an LNCaP subline that secretes IL-6, and LNCaP-C3, a control subline that does not express IL-6, were analyzed for IL-6-induced NED, activation of JAK2 and STAT3 pathways, and expression of IL-6/IL-6R signaling proteins and downstream target genes. RESULTS IL-6 did not induce NED in LNCaP-S17 cells, even though IL-6 induced NED in LNCaP-C3 cells. IL-6 activated JAK2 and STAT3 pathways in LNCaP-C3 cells but not in LNCaP-S17 cells. IL-6 did not activate ERK1/2, AKT, or NF-κB pathways in either cell line. Both LNCaP-C3 and LNCaP-S17 cell lines expressed IL-6R, gp130, and TYK2 at almost the same levels and did not express JAK1 or JAK3. The basal level of JAK2 expression was slightly higher in LNCaP-C3 cells than in LNCaP-S17 cells. Two suppressors of cytokine signaling, SOCS7 and cytokine-inducible SH2 protein (CIS), were expressed constitutively at higher levels in LNCaP-S17 cells than in LNCaP-C3 cells, while SOCS1 to SOCS6 were expressed at approximately the same levels. Using siRNA to knockdown SOCS7 and CIS expression in LNCaP-S17 cells led to increased phosphorylation of STAT3 upon IL-6 stimulation. CONCLUSIONS LNCaP-S17 cells are resistant to exogenous IL-6-induced NED due to increased levels of CIS/SOCS7 that block activation of JAK2-STAT3 pathways.

KW - IL-6

KW - neuroendocrine

KW - prostate cancer

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JF - Prostate

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