Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells.
BACKGROUND
Neuroendocrine (NE) differentiation in prostate cancer has been suggested to be one of the early events in the development of androgen independence. In the human prostate cancer LNCaP cell line, treatment with interleukin-6 (IL-6) induces NE-like differentiation, which is similar to the phenomena observed in advanced stages of prostate cancer progression. In this study, we investigate how androgen plays a role in IL-6-mediated NE differentiation in LNCaP cell line.


METHODS
Western blot, co-immunoprecipitation (co-IP), and GST pull-down assays were performed to detect the protein expression and protein-protein interaction. PI3K kinase assay was used to measure PI3K activity.


RESULTS
Addition of androgen blocks IL-6-mediated PI3K activation and NE differentiation in LNCaP cells. In vivo and in vitro protein interaction assays suggested that androgen receptor (AR) can directly interact with IL-6 transducer gp130. In addition, androgen treatment enhances the interaction between AR and gp130, interrupts the IL-6-induced gp130-mediated PI3K activation, which may lead to inhibition of IL-6-mediated NE differentiation in LNCaP cells.


CONCLUSIONS
Our results suggest androgen and AR can regulate IL-6-mediated LNCaP cell NE differentiation via directly modulating the IL-6-PI3K pathway.
Xie
Shaozhen
S
George H. Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester, Rochester, New York 14642, USA.
Lin
Hui-Kuan
HK
Ni
Jing
J
Yang
Lin
L
Wang
Liang
L
di Sant'Agnese
P Anthony
PA
Chang
Chawnshang
C
D015153:Blotting, Western; D002454:Cell Differentiation; D058966:Contactins; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D019006:Neural Cell Adhesion Molecules / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000494:pharmacology*; D010957:Plasmids; D011471:Prostatic Neoplasms / Q000473:pathology*; D011944:Receptors, Androgen / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D058966:Contactins; D015850:Interleukin-6; D019006:Neural Cell Adhesion Molecules; D011944:Receptors, Androgen; D019869:Phosphatidylinositol 3-Kinases