Androgens block interleukin-1β-induced promatrilysin expression in prostate carcinoma cells

M. Suzanne Stratton, Benjamin Greenstein, Thirupandiyur S. Udayakumar, Raymond B Nagle, G. Timothy Bowden

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND. We have shown previously that interleukin (IL) -1β- and IL-6-induced promatrilysin expression is mediated by an indirect pathway that requires NFκB-dependent synthesis of synthesisof IL-6 and STAT3 signaling. We now demonstrate that IL-1β-induced but not IL-6-induced promatrilysin expression can be blocked by androgens in the prostate carcinoma cell line LNCaP (lymph node-derived carcinoma cells of the prostate). METHODS. By using enzyme-linked immunosorbent assay analyses, promatrilysin was measured in LNCaP cells stimulated with IL-1β or IL-6 LNCaP-treated cells pretreated with testosterone. In addition, promatrilysin message was measured by using Northern analyses after IL-6-treated cells pretreated with testosterone. RESULTS. In LNCaP treated with testosterone before IL-1β stimulation induced promatrilysin expression was completely abrogated. Furthermore, testosterone completely abrogated NFκB transactivation activity and induction of IL-6 protein expression and mRNA. Testosterone and 5α-dihydrotestosterone did not have an inhibitory effect on IL-6-induced promatrilysin expression. Testosterone also had no effect on basal promatrilysin expression or basal NFκB transactivation activity. CONCLUSION. From these data, we conclude that testosterone blocks IL-1β-induced promatrilysin expression by inhibition of NFκB transactivation activity, which in turn, blocks IL-6 expression. These data suggest a mechanism in vivo by which invasive and metastatic prostatic carcinoma cell clones refractory to hormone ablation therapy may develop after chemical or surgical castration. Furthermore, these data suggest that, perhaps, upstream targets such as the cytokines IL-1β and IL-6 may provide alternative drug targets for inhibiting prostate cancer progression.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalProstate
Volume53
Issue number1
DOIs
StatePublished - Sep 15 2002

Fingerprint

Interleukin-1
Androgens
Prostate
Interleukin-6
Testosterone
Carcinoma
Lymph Nodes
Transcriptional Activation
promatrilysin
Dihydrotestosterone
Castration
Prostatic Neoplasms
Clone Cells
Enzyme-Linked Immunosorbent Assay
Hormones
Cytokines
Cell Line
Messenger RNA
Pharmaceutical Preparations

Keywords

  • Androgen
  • IL-1β
  • IL-6
  • Matrilysin

ASJC Scopus subject areas

  • Urology

Cite this

Androgens block interleukin-1β-induced promatrilysin expression in prostate carcinoma cells. / Stratton, M. Suzanne; Greenstein, Benjamin; Udayakumar, Thirupandiyur S.; Nagle, Raymond B; Bowden, G. Timothy.

In: Prostate, Vol. 53, No. 1, 15.09.2002, p. 1-8.

Research output: Contribution to journalArticle

Stratton, M. Suzanne ; Greenstein, Benjamin ; Udayakumar, Thirupandiyur S. ; Nagle, Raymond B ; Bowden, G. Timothy. / Androgens block interleukin-1β-induced promatrilysin expression in prostate carcinoma cells. In: Prostate. 2002 ; Vol. 53, No. 1. pp. 1-8.
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abstract = "BACKGROUND. We have shown previously that interleukin (IL) -1β- and IL-6-induced promatrilysin expression is mediated by an indirect pathway that requires NFκB-dependent synthesis of synthesisof IL-6 and STAT3 signaling. We now demonstrate that IL-1β-induced but not IL-6-induced promatrilysin expression can be blocked by androgens in the prostate carcinoma cell line LNCaP (lymph node-derived carcinoma cells of the prostate). METHODS. By using enzyme-linked immunosorbent assay analyses, promatrilysin was measured in LNCaP cells stimulated with IL-1β or IL-6 LNCaP-treated cells pretreated with testosterone. In addition, promatrilysin message was measured by using Northern analyses after IL-6-treated cells pretreated with testosterone. RESULTS. In LNCaP treated with testosterone before IL-1β stimulation induced promatrilysin expression was completely abrogated. Furthermore, testosterone completely abrogated NFκB transactivation activity and induction of IL-6 protein expression and mRNA. Testosterone and 5α-dihydrotestosterone did not have an inhibitory effect on IL-6-induced promatrilysin expression. Testosterone also had no effect on basal promatrilysin expression or basal NFκB transactivation activity. CONCLUSION. From these data, we conclude that testosterone blocks IL-1β-induced promatrilysin expression by inhibition of NFκB transactivation activity, which in turn, blocks IL-6 expression. These data suggest a mechanism in vivo by which invasive and metastatic prostatic carcinoma cell clones refractory to hormone ablation therapy may develop after chemical or surgical castration. Furthermore, these data suggest that, perhaps, upstream targets such as the cytokines IL-1β and IL-6 may provide alternative drug targets for inhibiting prostate cancer progression.",
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AU - Stratton, M. Suzanne

AU - Greenstein, Benjamin

AU - Udayakumar, Thirupandiyur S.

AU - Nagle, Raymond B

AU - Bowden, G. Timothy

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N2 - BACKGROUND. We have shown previously that interleukin (IL) -1β- and IL-6-induced promatrilysin expression is mediated by an indirect pathway that requires NFκB-dependent synthesis of synthesisof IL-6 and STAT3 signaling. We now demonstrate that IL-1β-induced but not IL-6-induced promatrilysin expression can be blocked by androgens in the prostate carcinoma cell line LNCaP (lymph node-derived carcinoma cells of the prostate). METHODS. By using enzyme-linked immunosorbent assay analyses, promatrilysin was measured in LNCaP cells stimulated with IL-1β or IL-6 LNCaP-treated cells pretreated with testosterone. In addition, promatrilysin message was measured by using Northern analyses after IL-6-treated cells pretreated with testosterone. RESULTS. In LNCaP treated with testosterone before IL-1β stimulation induced promatrilysin expression was completely abrogated. Furthermore, testosterone completely abrogated NFκB transactivation activity and induction of IL-6 protein expression and mRNA. Testosterone and 5α-dihydrotestosterone did not have an inhibitory effect on IL-6-induced promatrilysin expression. Testosterone also had no effect on basal promatrilysin expression or basal NFκB transactivation activity. CONCLUSION. From these data, we conclude that testosterone blocks IL-1β-induced promatrilysin expression by inhibition of NFκB transactivation activity, which in turn, blocks IL-6 expression. These data suggest a mechanism in vivo by which invasive and metastatic prostatic carcinoma cell clones refractory to hormone ablation therapy may develop after chemical or surgical castration. Furthermore, these data suggest that, perhaps, upstream targets such as the cytokines IL-1β and IL-6 may provide alternative drug targets for inhibiting prostate cancer progression.

AB - BACKGROUND. We have shown previously that interleukin (IL) -1β- and IL-6-induced promatrilysin expression is mediated by an indirect pathway that requires NFκB-dependent synthesis of synthesisof IL-6 and STAT3 signaling. We now demonstrate that IL-1β-induced but not IL-6-induced promatrilysin expression can be blocked by androgens in the prostate carcinoma cell line LNCaP (lymph node-derived carcinoma cells of the prostate). METHODS. By using enzyme-linked immunosorbent assay analyses, promatrilysin was measured in LNCaP cells stimulated with IL-1β or IL-6 LNCaP-treated cells pretreated with testosterone. In addition, promatrilysin message was measured by using Northern analyses after IL-6-treated cells pretreated with testosterone. RESULTS. In LNCaP treated with testosterone before IL-1β stimulation induced promatrilysin expression was completely abrogated. Furthermore, testosterone completely abrogated NFκB transactivation activity and induction of IL-6 protein expression and mRNA. Testosterone and 5α-dihydrotestosterone did not have an inhibitory effect on IL-6-induced promatrilysin expression. Testosterone also had no effect on basal promatrilysin expression or basal NFκB transactivation activity. CONCLUSION. From these data, we conclude that testosterone blocks IL-1β-induced promatrilysin expression by inhibition of NFκB transactivation activity, which in turn, blocks IL-6 expression. These data suggest a mechanism in vivo by which invasive and metastatic prostatic carcinoma cell clones refractory to hormone ablation therapy may develop after chemical or surgical castration. Furthermore, these data suggest that, perhaps, upstream targets such as the cytokines IL-1β and IL-6 may provide alternative drug targets for inhibiting prostate cancer progression.

KW - Androgen

KW - IL-1β

KW - IL-6

KW - Matrilysin

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DO - 10.1002/pros.10123

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