Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate cancer cell lines and inhibits androgen-mediated proliferation and secretion

Hannes Neuwirt, Martin Puhr, Ilaria T. Cavarretta, Michael Mitterberger, Alfred Hobisch, Zoran Culig

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Suppressors of cytokine signalling (SOCS) are induced by interleukins (ILs) and various peptide hormones and may prevent sustained activation of signalling pathways. We have previously shown that SOCS-3 antagonizes regulation of cellular events by cAMP and is expressed in human prostate cancer. To investigate possible effects of androgen on SOCS-3 protein expression, two prostate cancer cell lines (PC3-AR and LAPC4) were treated with different concentrations of R1881. Western blot analyses revealed induction of SOCS-3 protein expression in both cell lines by androgen, an effect which can be blocked by the anti-androgen bicalutamide. To further characterize the effects of R1881 on the SOCS-3 gene, promoter-reporter assay and real-time PCR were performed. We found no influence of androgen on promoter activity or SOCS-3 mRNA levels, thus suggesting a post-transcriptional effect of androgen. Concordant with our previous findings, we show a significant increase of SOCS-3 protein after androgen treatment in cells in which transcription was blocked, but not in those with impaired translation. In order to understand implications of SOCS-3 regulation by androgen, we used SOCS-3-negative LNCaP-IL-6 cells and stably transfected them with a tetracycline-responsive SOCS-3 Tet-On plasmid. We report that androgenic effects on cell proliferation and prostate-specific antigen secretion are significantly diminished following up-regulation of SOCS-3. In conclusion, androgen up-regulates SOCS-3 protein via post-transcriptional effects. SOCS-3 inhibits androgen-stimulated proliferation by influencing cell cycle regulation. Taken together with previous findings showing androgen receptor activation by IL-6, our results imply that androgen and cytokine signalling pathways interact at multiple levels in prostate cancer.

Original languageEnglish
Pages (from-to)1007-1019
Number of pages13
JournalEndocrine-Related Cancer
Volume14
Issue number4
DOIs
Publication statusPublished - Dec 2007

Fingerprint

Androgens
Prostatic Neoplasms
Cytokines
Cell Line
Metribolone
Interleukin-6
Up-Regulation
Peptide Hormones
Interleukins
Androgen Receptors
Prostate-Specific Antigen
Tetracycline
Reporter Genes
Real-Time Polymerase Chain Reaction
Cell Cycle
Plasmids
Western Blotting
Cell Proliferation
Messenger RNA
Suppressor of Cytokine Signaling 3 Protein

ASJC Scopus subject areas

  • Cancer Research
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Oncology

Cite this

Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate cancer cell lines and inhibits androgen-mediated proliferation and secretion. / Neuwirt, Hannes; Puhr, Martin; Cavarretta, Ilaria T.; Mitterberger, Michael; Hobisch, Alfred; Culig, Zoran.

In: Endocrine-Related Cancer, Vol. 14, No. 4, 12.2007, p. 1007-1019.

Research output: Contribution to journalArticle

Neuwirt, Hannes ; Puhr, Martin ; Cavarretta, Ilaria T. ; Mitterberger, Michael ; Hobisch, Alfred ; Culig, Zoran. / Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate cancer cell lines and inhibits androgen-mediated proliferation and secretion. In: Endocrine-Related Cancer. 2007 ; Vol. 14, No. 4. pp. 1007-1019.
@article{fd7067e55de241a98c58cc5a9fde1ea8,
title = "Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate cancer cell lines and inhibits androgen-mediated proliferation and secretion",
abstract = "Suppressors of cytokine signalling (SOCS) are induced by interleukins (ILs) and various peptide hormones and may prevent sustained activation of signalling pathways. We have previously shown that SOCS-3 antagonizes regulation of cellular events by cAMP and is expressed in human prostate cancer. To investigate possible effects of androgen on SOCS-3 protein expression, two prostate cancer cell lines (PC3-AR and LAPC4) were treated with different concentrations of R1881. Western blot analyses revealed induction of SOCS-3 protein expression in both cell lines by androgen, an effect which can be blocked by the anti-androgen bicalutamide. To further characterize the effects of R1881 on the SOCS-3 gene, promoter-reporter assay and real-time PCR were performed. We found no influence of androgen on promoter activity or SOCS-3 mRNA levels, thus suggesting a post-transcriptional effect of androgen. Concordant with our previous findings, we show a significant increase of SOCS-3 protein after androgen treatment in cells in which transcription was blocked, but not in those with impaired translation. In order to understand implications of SOCS-3 regulation by androgen, we used SOCS-3-negative LNCaP-IL-6 cells and stably transfected them with a tetracycline-responsive SOCS-3 Tet-On plasmid. We report that androgenic effects on cell proliferation and prostate-specific antigen secretion are significantly diminished following up-regulation of SOCS-3. In conclusion, androgen up-regulates SOCS-3 protein via post-transcriptional effects. SOCS-3 inhibits androgen-stimulated proliferation by influencing cell cycle regulation. Taken together with previous findings showing androgen receptor activation by IL-6, our results imply that androgen and cytokine signalling pathways interact at multiple levels in prostate cancer.",
author = "Hannes Neuwirt and Martin Puhr and Cavarretta, {Ilaria T.} and Michael Mitterberger and Alfred Hobisch and Zoran Culig",
year = "2007",
month = "12",
doi = "10.1677/ERC-07-0172",
language = "English",
volume = "14",
pages = "1007--1019",
journal = "Endocrine-Related Cancer",
issn = "1351-0088",
publisher = "BioScientifica Ltd.",
number = "4",

}

TY - JOUR

T1 - Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate cancer cell lines and inhibits androgen-mediated proliferation and secretion

AU - Neuwirt, Hannes

AU - Puhr, Martin

AU - Cavarretta, Ilaria T.

AU - Mitterberger, Michael

AU - Hobisch, Alfred

AU - Culig, Zoran

PY - 2007/12

Y1 - 2007/12

N2 - Suppressors of cytokine signalling (SOCS) are induced by interleukins (ILs) and various peptide hormones and may prevent sustained activation of signalling pathways. We have previously shown that SOCS-3 antagonizes regulation of cellular events by cAMP and is expressed in human prostate cancer. To investigate possible effects of androgen on SOCS-3 protein expression, two prostate cancer cell lines (PC3-AR and LAPC4) were treated with different concentrations of R1881. Western blot analyses revealed induction of SOCS-3 protein expression in both cell lines by androgen, an effect which can be blocked by the anti-androgen bicalutamide. To further characterize the effects of R1881 on the SOCS-3 gene, promoter-reporter assay and real-time PCR were performed. We found no influence of androgen on promoter activity or SOCS-3 mRNA levels, thus suggesting a post-transcriptional effect of androgen. Concordant with our previous findings, we show a significant increase of SOCS-3 protein after androgen treatment in cells in which transcription was blocked, but not in those with impaired translation. In order to understand implications of SOCS-3 regulation by androgen, we used SOCS-3-negative LNCaP-IL-6 cells and stably transfected them with a tetracycline-responsive SOCS-3 Tet-On plasmid. We report that androgenic effects on cell proliferation and prostate-specific antigen secretion are significantly diminished following up-regulation of SOCS-3. In conclusion, androgen up-regulates SOCS-3 protein via post-transcriptional effects. SOCS-3 inhibits androgen-stimulated proliferation by influencing cell cycle regulation. Taken together with previous findings showing androgen receptor activation by IL-6, our results imply that androgen and cytokine signalling pathways interact at multiple levels in prostate cancer.

AB - Suppressors of cytokine signalling (SOCS) are induced by interleukins (ILs) and various peptide hormones and may prevent sustained activation of signalling pathways. We have previously shown that SOCS-3 antagonizes regulation of cellular events by cAMP and is expressed in human prostate cancer. To investigate possible effects of androgen on SOCS-3 protein expression, two prostate cancer cell lines (PC3-AR and LAPC4) were treated with different concentrations of R1881. Western blot analyses revealed induction of SOCS-3 protein expression in both cell lines by androgen, an effect which can be blocked by the anti-androgen bicalutamide. To further characterize the effects of R1881 on the SOCS-3 gene, promoter-reporter assay and real-time PCR were performed. We found no influence of androgen on promoter activity or SOCS-3 mRNA levels, thus suggesting a post-transcriptional effect of androgen. Concordant with our previous findings, we show a significant increase of SOCS-3 protein after androgen treatment in cells in which transcription was blocked, but not in those with impaired translation. In order to understand implications of SOCS-3 regulation by androgen, we used SOCS-3-negative LNCaP-IL-6 cells and stably transfected them with a tetracycline-responsive SOCS-3 Tet-On plasmid. We report that androgenic effects on cell proliferation and prostate-specific antigen secretion are significantly diminished following up-regulation of SOCS-3. In conclusion, androgen up-regulates SOCS-3 protein via post-transcriptional effects. SOCS-3 inhibits androgen-stimulated proliferation by influencing cell cycle regulation. Taken together with previous findings showing androgen receptor activation by IL-6, our results imply that androgen and cytokine signalling pathways interact at multiple levels in prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=39149125783&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39149125783&partnerID=8YFLogxK

U2 - 10.1677/ERC-07-0172

DO - 10.1677/ERC-07-0172

M3 - Article

VL - 14

SP - 1007

EP - 1019

JO - Endocrine-Related Cancer

JF - Endocrine-Related Cancer

SN - 1351-0088

IS - 4

ER -