Genistein differentially modulates androgen-responsive gene expression and activates JNK in LNCaP cells

  • Authors:
    • Bato Lazarevic
    • Steinar Johan Karlsen
    • Fahri Saatcioglu
  • View Affiliations

  • Published online on: May 1, 2008     https://doi.org/10.3892/or.19.5.1231
  • Pages: 1231-1235
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Genistein, the predominant isoflavone in soy, may be chemopreventive in prostate cancer (CaP). It down-regulates the prostate-specific antigen (PSA) and androgen receptor (AR) in androgen responsive cells. However, the extent of the down-regulation and whether genistein has a general effect on all androgen responsive genes (ARGs) are unclear. We investigated the ability of genistein to modulate ARG expression by the synthetic androgen R1881 in LNCaP cells. Given that there is important crosstalk between AR and mitogen activated protein kinase (MAPK) signaling, we also investigated whether genistein activates the MAPK end targets c-Jun N-terminal kinase (JNK) and c-Jun. Changes in ARG expression were determined by Western analysis and semi-quantitative RT-PCR. The activation of JNK and c-Jun was investigated by Western analysis and a solid phase kinase assay. The PSA protein and mRNA expression were both down-regulated by genistein. In contrast, KLK4 was up-regulated at the mRNA, but down-regulated at the protein level. NKX3.1 mRNA levels did not change significantly, but protein levels were significantly down-regulated. STAMP2 mRNA levels slightly increased whereas the protein expression was down-regulated. The AR mRNA expression changed significantly only at high concentrations of genistein when it was down-regulated, whereas AR protein levels were decreased at low concentrations of genistein. The solid phase kinase assay indicated a transient activation of JNK by genistein, which was supported by Western analysis. Thus genistein differentially modulates ARG mRNA expression, but has an inhibitory role on the ARG protein levels. The activation of the JNK pathway which inhibits AR signaling may provide a mechanism for the overall inhibition of protein levels.

Related Articles

Journal Cover

May 2008
Volume 19 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Lazarevic, B., Karlsen, S.J., & Saatcioglu, F. (2008). Genistein differentially modulates androgen-responsive gene expression and activates JNK in LNCaP cells. Oncology Reports, 19, 1231-1235. https://doi.org/10.3892/or.19.5.1231
MLA
Lazarevic, B., Karlsen, S. J., Saatcioglu, F."Genistein differentially modulates androgen-responsive gene expression and activates JNK in LNCaP cells". Oncology Reports 19.5 (2008): 1231-1235.
Chicago
Lazarevic, B., Karlsen, S. J., Saatcioglu, F."Genistein differentially modulates androgen-responsive gene expression and activates JNK in LNCaP cells". Oncology Reports 19, no. 5 (2008): 1231-1235. https://doi.org/10.3892/or.19.5.1231