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

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.
Mesh Terms:
Blotting, Western, Cell Cycle Proteins, Cell Division, Cell Size, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases, Cyclins, G1 Phase, Gene Expression Regulation, Histones, Humans, Interleukin-6, Male, Microtubule-Associated Proteins, Neurons, Precipitin Tests, Prostatic Neoplasms, Protein Binding, Retinoblastoma Protein, Time Factors, Tumor Cells, Cultured, Tumor Suppressor Proteins
Biochem. Biophys. Res. Commun.
Date: Apr. 13, 1999
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