Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin-dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate tumor cells

Biochem Biophys Res Commun. 1999 Apr 13;257(2):609-14. doi: 10.1006/bbrc.1999.0515.


Prostate carcinoma cells express high levels of interleukin-6 (IL-6) and IL-6 receptor. In this study, we examined the effect of IL-6 on LNCaP human prostate carcinoma cells. IL-6 induces G1 growth arrest of LNCaP. Following IL-6 treatment of LNCaP, Western blot analysis showed that the protein levels of cyclin-dependent kinase-2 (CDK2), CDK4, and CDK6 were decreased, while accumulation of CDK inhibitor p27(Kip1) was rapidly and markedly induced. In vitro kinase assays revealed that the CDK-associated histone H1 and CDK4- and CDK6-associated pRb kinase activities were significantly inhibited in IL-6-treated LNCaP. Further, a significant amount of p27(Kip1) was co-precipitated with CDK2, CDK4 and CDK6, as detected in immunoprecipitation experiments. Thus, IL-6-induced G1 arrest appears to be due to the accumulation of p27(Kip1). In addition, IL-6-treated LNCaP cells induced neuron-like morphological changes. Since neuroendocrine differentiation is observed in most prostate carcinomas, these findings raise the possibility that IL-6 may be involved in neuroendocrine differentiation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Cycle Proteins*
  • Cell Division / drug effects
  • Cell Size / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / metabolism
  • G1 Phase / drug effects*
  • Gene Expression Regulation / drug effects
  • Histones / metabolism
  • Humans
  • Interleukin-6 / pharmacology*
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Neurons / cytology*
  • Precipitin Tests
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein Binding / drug effects
  • Retinoblastoma Protein / metabolism
  • Time Factors
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*


  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Histones
  • Interleukin-6
  • Microtubule-Associated Proteins
  • Retinoblastoma Protein
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases