TY - JOUR
T1 - Interleukin-6 induces prostate cancer cell growth accompanied by activation of Stat3 signaling pathway
AU - Lou, Wei
AU - Ni, Zuyao
AU - Dyer, Kevin
AU - Tweardy, David J.
AU - Gao, Allen C
PY - 2000/2/15
Y1 - 2000/2/15
N2 - BACKGROUND. Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates growth and differentiation of various types of malignant tumors, including prostate carcinomas. The levels of IL-6 are elevated in sera of patients with metastatic prostate cancer. In this study, we evaluate the role of IL-6 in the growth regulation of prostate cancer cells. METHODS. Expression of IL-6 and its receptors in human prostate cancer cells was measured by ELISA and RT-PCR. The effects of IL-6 on cell growth were evaluated by ectopically expressing IL-6 cDNA into IL-6-negative LNCaP human prostate cancer cells. Stat3 DNA binding activities were analyzed by electromobility shift assay and supershift assay. RESULTS. Expression of IL-6 was detected in the androgen-insensitive prostate cancer cell lines (i.e., TSU, PC3, and DU145), but not in the androgen-sensitive LNCaP cell line. IL-6 receptors, including both IL-6-specific receptor α chain and gp130 signal transducer, are expressed in all human prostate cancer cell lines (i.e., LNCaP, TSU, PC3, and DU145). Overexpression of IL-6 by ectopically expressing IL-6 into IL-6-negative LNCaP human prostate cancer cells significantly increased clonogenic ability and cell proliferation in vitro compared to the IL-6-negative parental LNCaP cells and the antisense controls. This growth stimulation by IL-6 was accompanied by activation of the Stat3 signaling transduction pathway. CONCLUSIONS. IL-6 is an autocrine growth factor for LNCaP human prostate cancer cells; the effects of IL-6 on prostate cancer cell growth are mediated through the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway. (C) 2000 Wiley- Liss, Inc.
AB - BACKGROUND. Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates growth and differentiation of various types of malignant tumors, including prostate carcinomas. The levels of IL-6 are elevated in sera of patients with metastatic prostate cancer. In this study, we evaluate the role of IL-6 in the growth regulation of prostate cancer cells. METHODS. Expression of IL-6 and its receptors in human prostate cancer cells was measured by ELISA and RT-PCR. The effects of IL-6 on cell growth were evaluated by ectopically expressing IL-6 cDNA into IL-6-negative LNCaP human prostate cancer cells. Stat3 DNA binding activities were analyzed by electromobility shift assay and supershift assay. RESULTS. Expression of IL-6 was detected in the androgen-insensitive prostate cancer cell lines (i.e., TSU, PC3, and DU145), but not in the androgen-sensitive LNCaP cell line. IL-6 receptors, including both IL-6-specific receptor α chain and gp130 signal transducer, are expressed in all human prostate cancer cell lines (i.e., LNCaP, TSU, PC3, and DU145). Overexpression of IL-6 by ectopically expressing IL-6 into IL-6-negative LNCaP human prostate cancer cells significantly increased clonogenic ability and cell proliferation in vitro compared to the IL-6-negative parental LNCaP cells and the antisense controls. This growth stimulation by IL-6 was accompanied by activation of the Stat3 signaling transduction pathway. CONCLUSIONS. IL-6 is an autocrine growth factor for LNCaP human prostate cancer cells; the effects of IL-6 on prostate cancer cell growth are mediated through the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway. (C) 2000 Wiley- Liss, Inc.
KW - IL-6
KW - Prostate cancer
KW - Signaling pathway
KW - STAT
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U2 - 10.1002/(SICI)1097-0045(20000215)42:3<239::AID-PROS10>3.0.CO;2-G
DO - 10.1002/(SICI)1097-0045(20000215)42:3<239::AID-PROS10>3.0.CO;2-G
M3 - Article
C2 - 10639195
AN - SCOPUS:0034651980
VL - 42
SP - 239
EP - 242
JO - Prostate
JF - Prostate
SN - 0270-4137
IS - 3
ER -