RT Journal Article
SR Electronic
T1 Interleukin-4 in Patients with Prostate Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4595
OP 4598
VO 25
IS 6C
A1 TAKESHI UEDA
A1 MARIANNE D. SADAR
A1 HIROYOSHI SUZUKI
A1 KOICHIRO AKAKURA
A1 SHINICHI SAKAMOTO
A1 MASAKI SHIMBO
A1 TAKAHITO SUYAMA
A1 TAKASHI IMAMOTO
A1 AKIRA KOMIYA
A1 NAYA YUKIO
A1 TOMOHIKO ICHIKAWA
YR 2005
UL http://ar.iiarjournals.org/content/25/6C/4595.abstract
AB Background: Ligand-independent activation of the androgen receptor (AR) by cytokines has been implicated in the progression of androgen-independent prostate cancer (PCa). To determine the potential effects of elevated levels of interleukin-4 (IL-4) in patients with PCa, six different cytokines were examined for their ability to activate the AR. Materials and Methods: LNCaP cells were transiently transfected with prostate-specific antigen (PSA) (-630/+12)-luciferase and treated with R1881, six kinds of cytokines including IL-4, or vehicle. Transactivation assays were also performed in LNCaP cells co-transfected with the 5xGal4UAS-TATA-luciferase and AR-(1-558)-Gal4DBD prior to incubation with R1881, IL-4, IL-6, or vehicle. Seventy-two patients with pre-treatment PCa, 17 patients with hormone-refractory metastatic PCa receiving androgen ablation therapy, 20 patients with benign prostatic hypertrophy and 10 healthy male volunteers were enrolled in this retrospective study. The concentration of serum IL-4 was measured by chemiluminescence enzyme immunoassay. Results: IL-4 induced androgen-response element-driven reporters and activated the AR N-terminal domain (NTD) in a ligand-independent manner in transiently transfected LNCaP cells. Levels of IL-4 in the serum were significantly elevated in patients with hormone-refractory PCa as compared to the levels in pre-treatment PCa. Conclusion: IL-4 serum levels were demonstrated to be increased in hormone-refractory PCa and IL-4 was shown to enhance PSA reporter gene activity by the activation of AR NTD in human LNCaP cells. These results suggest that the AR can be activated by cytokines, and that this mechanism may play an important role in the transition from androgen-dependent to androgen-independent PCa after patients receive androgen ablation therapy. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved