Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway

Prostate. 2000 Feb 15;42(3):239-42. doi: 10.1002/(sici)1097-0045(20000215)42:3<239::aid-pros10>;2-g.


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 alpha 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / biosynthesis
  • Cell Division / physiology
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / physiology*
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Prostatic Neoplasms / pathology*
  • Receptors, Interleukin-6 / biosynthesis
  • STAT3 Transcription Factor
  • Signal Transduction / physiology*
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured


  • Antigens, CD
  • DNA-Binding Proteins
  • IL6ST protein, human
  • Interleukin-6
  • Membrane Glycoproteins
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Cytokine Receptor gp130