Abstract |
Several reports suggest that androgen signalling interferes with canonical RelA-p50 activity in androgen-sensitive cells. Whether this also occurs with non-canonical NF-kappaB subunits has not been studied. Here we report that androgenic stimulation of LNCaP cells with the androgen analogue R1881 appears to positively regulate the non-canonical NF-kappaB pathway as p52 accumulates both in the cytoplasm and nucleus after 48-72 h of stimulation. In contrast to TNF-alpha stimulation, androgen stimulation fails to induce RelB expression and is absent from nucleus of R1881-treated LNCaP cells. Electromobility shift assays reveal a time-dependent change in the nature of NF-kappaB complexes actively bound to DNA after 72 h of androgenic stimulation concomitant with the appearance of p52-containing complexes. Co-immunoprecipitation studies indicate that newly produced p52 can exist as a heterodimer with RelA or p50, but may be mainly present as a homodimer. RNAi experiments targeting IKK-alpha and IKK-beta show that the R1881-induced nuclear accumulation of p52 is IKK-alpha-dependent. These results point to a novel mechanism by which androgens regulate NF-kappaB and provide a rationale for further studies into the biological significance of non-canonical NF-kappaB signalling in prostate cancer.
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Authors | Laurent Lessard, Fred Saad, Cécile Le Page, Jean-Simon Diallo, Benjamin Péant, Nathalie Delvoye, Anne-Marie Mes-Masson |
Journal | Cellular signalling
(Cell Signal)
Vol. 19
Issue 5
Pg. 1093-100
(May 2007)
ISSN: 0898-6568 [Print] England |
PMID | 17292587
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Androgens
- NF-kappa B p50 Subunit
- NF-kappa B p52 Subunit
- Receptors, Androgen
- Testosterone Congeners
- Transcription Factor RelA
- Metribolone
- CHUK protein, human
- I-kappa B Kinase
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Topics |
- Androgens
(metabolism)
- Cell Line, Tumor
- Cell Nucleus
(metabolism)
- Cytoplasm
(metabolism)
- Humans
- I-kappa B Kinase
(metabolism)
- Male
- Metribolone
(pharmacology)
- NF-kappa B p50 Subunit
(metabolism)
- NF-kappa B p52 Subunit
(metabolism)
- Prostatic Neoplasms
(metabolism)
- Receptors, Androgen
(metabolism)
- Signal Transduction
- Testosterone Congeners
(pharmacology)
- Transcription Factor RelA
(metabolism)
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