| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Unit for Laboratory Animal Medicine [D-L. L., M. C. W., E. T. K.], Department of Pathology [E. T. K.], Program in Cellular and Molecular Biology [E. T. K.], and Institute of Gerontology [E. T. K.], University of Michigan, Ann Arbor, Michigan 48109, and Department of Immunology, Tianjin Medical University, Tianjin, China 300203 [Z.Y.]
Interleukin-6 (IL-6) induces prostate cancer (CaP) cell proliferation in vitro. Several lines of evidence suggest that IL-6 may promote CaP progression through induction of an androgen response. In this work, we explored whether IL-6 induces androgen responsiveness through modulation of androgen receptor (AR) expression. We found that in the absence of androgen, IL-6 increased prostate-specific antigen (PSA) mRNA levels and activated several androgen-responsive promoters, but not the non-androgen responsive promoters in LNCaP cells. Bicalutamide, an antiandrogen, abolished the IL-6 effect and IL-6 could not activate the PSA and murine mammary tumor virus reporters in AR-negative DU-145 and PC3 cells. These data indicate the IL-6 induces an androgen response in CaP cells through the AR. Pretreatment of LNCaP cells with SB202190, PD98059, or tyrphostin AG879 [p38 mitogen-activated protein kinase (MAPK), MAP/extracellular signal-regulated protein kinase kinase 1/2, and ErbB2 MAPK inhibitors, respectively) but not wortmannin (PI3-kinase inhibitor) blocked IL-6-mediated induction of the PSA promoter, which demonstrates that IL-6 activity is dependent on a MAPK pathway. Finally, IL-6 activated the AR gene promoter, resulting in increased AR mRNA and protein levels in LNCaP cells. These results demonstrate that IL-6 induces AR expression and are the first report of cytokine-mediated induction of the AR promoter. Taken together, our results suggest that IL-6 induces AR activity through both increasing AR gene expression and activating the AR in the absence of androgen in CaP cells. These results provide a mechanism through which IL-6 may contribute to the development of androgen-independent CaP.
This article has been cited by other articles:
|
|
 |
|
  N. E. Gray, X. Liu, R. Choi, M. R. Blackman, and J. T. Arnold Endocrine-Immune-Paracrine Interactions in Prostate Cells as Targeted by Phytomedicines Cancer Prevention Research, February 1, 2009; 2(2): 134 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kanda, R. Steele, R. Ray, and R. B. Ray Hepatitis C Virus Core Protein Augments Androgen Receptor-Mediated Signaling J. Virol., November 15, 2008; 82(22): 11066 - 11072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-H. Tsui, T.-H. Feng, C.-M. Lin, P.-L. Chang, and H.-H. Juang Curcumin Blocks the Activation of Androgen and Interlukin-6 on Prostate-Specific Antigen Expression in Human Prostatic Carcinoma Cells J Androl, November 1, 2008; 29(6): 661 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Neuwirt, M. Puhr, I. T Cavarretta, M. Mitterberger, A. Hobisch, and Z. Culig Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate cancer cell lines and inhibits androgen-mediated proliferation and secretion Endocr. Relat. Cancer, December 1, 2007; 14(4): 1007 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Riera, M. N. Galardo, E. H. Pellizzari, S. B. Meroni, and S. B. Cigorraga Participation of phosphatidyl inositol 3-kinase/protein kinase B and ERK1/2 pathways in interleukin-1{beta} stimulation of lactate production in Sertoli cells Reproduction, April 1, 2007; 133(4): 763 - 773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Heer, A. T. Collins, C. N. Robson, B. K. Shenton, and H. Y. Leung KGF suppresses {alpha}2{beta}1 integrin function and promotes differentiation of the transient amplifying population in human prostatic epithelium. J. Cell Sci., April 1, 2006; 119(Pt 7): 1416 - 1424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. E. MacRae, C. Farquharson, and S. F. Ahmed The pathophysiology of the growth plate in juvenile idiopathic arthritis Rheumatology, January 1, 2006; 45(1): 11 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, S. Majumder, W. McCall, C. I. Sartor, J. L. Mohler, C. W. Gregory, H. S. Earp, and Y. E. Whang Inhibition of HER-2/neu Kinase Impairs Androgen Receptor Recruitment to the Androgen Responsive Enhancer Cancer Res., April 15, 2005; 65(8): 3404 - 3409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. George, S. Halabi, T. F. Shepard, B. Sanford, N. J. Vogelzang, E. J. Small, and P. W. Kantoff The Prognostic Significance of Plasma Interleukin-6 Levels in Patients with Metastatic Hormone-Refractory Prostate Cancer: Results from Cancer and Leukemia Group B 9480 Clin. Cancer Res., March 1, 2005; 11(5): 1815 - 1820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. McCarty Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy Integr Cancer Ther, December 1, 2004; 3(4): 349 - 380. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Tong and H.-H. Tai Synergistic Induction of the Nicotinamide Adenine Dinucleotide-Linked 15-Hydroxyprostaglandin Dehydrogenase by an Androgen and Interleukin-6 or Forskolin in Human Prostate Cancer Cells Endocrinology, May 1, 2004; 145(5): 2141 - 2147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Heinlein and C. Chang Androgen Receptor in Prostate Cancer Endocr. Rev., April 1, 2004; 25(2): 276 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Jia, C. S-Y. Choong, C. Ricciardelli, J. Kim, W. D. Tilley, and G. A Coetzee Androgen Receptor Signaling: Mechanism of Interleukin-6 Inhibition Cancer Res., April 1, 2004; 64(7): 2619 - 2626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Dong, S. O. Lee, H. Zhang, J. Marshall, A. C. Gao, and C. Ip Prostate Specific Antigen Expression Is Down-Regulated by Selenium through Disruption of Androgen Receptor Signaling Cancer Res., January 1, 2004; 64(1): 19 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Steiner, S. Godoy-Tundidor, H. Rogatsch, A. P. Berger, D. Fuchs, B. Comuzzi, G. Bartsch, A. Hobisch, and Z. Culig Accelerated in Vivo Growth of Prostate Tumors that Up-Regulate Interleukin-6 Is Associated with Reduced Retinoblastoma Protein Expression and Activation of the Mitogen-Activated Protein Kinase Pathway Am. J. Pathol., February 1, 2003; 162(2): 655 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. O. Lee, W. Lou, M. Hou, F. de Miguel, L. Gerber, and A. C. Gao Interleukin-6 Promotes Androgen-independent Growth in LNCaP Human Prostate Cancer Cells Clin. Cancer Res., January 1, 2003; 9(1): 370 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Debes, L. J. Schmidt, H. Huang, and D. J. Tindall p300 Mediates Androgen-independent Transactivation of the Androgen Receptor by Interleukin 6 Cancer Res., October 15, 2002; 62(20): 5632 - 5636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Godoy-Tundidor, A. Hobisch, K. Pfeil, G. Bartsch, and Z. Culig Acquisition of Agonistic Properties of Nonsteroidal Antiandrogens after Treatment with Oncostatin M in Prostate Cancer Cells Clin. Cancer Res., July 1, 2002; 8(7): 2356 - 2361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ueda, N. Bruchovsky, and M. D. Sadar Activation of the Androgen Receptor N-terminal Domain by Interleukin-6 via MAPK and STAT3 Signal Transduction Pathways J. Biol. Chem., February 22, 2002; 277(9): 7076 - 7085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-Y. Yu-Lee Prolactin Modulation of Immune and Inflammatory Responses Recent Prog. Horm. Res., January 1, 2002; 57(1): 435 - 455. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
