Dexamethasone enhances expression of membrane and soluble interleukin-6 receptors by prostate carcinoma cell lines.
BACKGROUND
Primary prostate carcinoma cells constitutively secrete interleukin-6 (IL-6), and high levels of IL-6 receptor are detected in prostate carcinoma tissues. These findings have implicated IL-6 in the growth and differentiation of prostate carcinomas. Herein, we examined the regulation of IL-6 receptor complex (IL-6R alpha/gpl30) in prostate carcinoma cell lines. We also analyzed the production of soluble IL-6R alpha (IL-6sR) because IL-6sR can confer the IL-6 responsiveness on IL-6R alpha-lacking cells.


METHODS
Three established prostate carcinoma cell lines, PC-3, DU 145 and LNCaP, were analyzed. Protein tyrosine-phosphorylation was detected by immunoblotting. The expression of IL-6R alpha, gpl30 and IL-6sR was determined by RT-PCR, flow cytometry and ELISA.


RESULTS
IL-6 induced tyrosine-phosphorylated proteins in LNCaP but not in PC-3 or DU 145, indicating that LNCaP cells express the functional IL-6 receptor. Dexamethasone (Dex)-treatment induced functional IL-6 receptors on DU 145 and PC-3 through upregulation of IL-6R alpha and gpl30. In addition, LNCaP, Dex-treated PC-3 and Dex-treated DU 145 secreted large amounts of IL-6sR.


CONCLUSIONS
The expression of IL-6 receptor by prostate carcinoma cell lines was augmented by glucocorticoid. We propose prostate carcinomas as IL-6sR producing tumors, and IL-6sR may modulate the behavior of not only the tumor cells but also the surrounding cells.
Mori
S
S
Department of Microbiology and Immunology, UCLA School of Medicine 90095-1747, USA.
Murakami-Mori
K
K
Bonavida
B
B
D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D017077:Culture Media, Conditioned; D003907:Dexamethasone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D017077:Culture Media, Conditioned; D010750:Phosphoproteins; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D019000:Phosphotyrosine; D003907:Dexamethasone