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J Carcinog. 2007 Apr 19;6:5.

Persistent activation of NF-kappaB related to IkappaB's degradation profiles during early chemical hepatocarcinogenesis.

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1
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, México DF, México. bky@cell.cinvestav.mx

Abstract

BACKGROUND:

To define the NF-kappaB activation in early stages of hepatocarcinogenesis and its IkappaB's degradation profiles in comparison to sole liver regeneration.

METHODS:

Western-blot and EMSA analyses were performed for the NF-kappaB activation. The transcriptional activity of NF-kappaB was determined by RT-PCR of the IkappaB-alpha mRNA. The IkappaB's degradation proteins were determined by Western-blot assay.

RESULTS:

We demonstrated the persistent activation of NF-kappaB during early stages of hepatocarcinogenesis, which reached maximal level 30 min after partial hepatectomy. The DNA binding and transcriptional activity of NF-kappaB, were sustained during early steps of hepatocarcinogenesis in comparison to only partial hepatectomy, which displayed a transitory NF-kappaB activation. In early stages of hepatocarcinogenesis, the IkappaB-alpha degradation turned out to be acute and transitory, but the low levels of IkappaB-beta persisted even 15 days after partial hepatectomy. Interestingly, IkappaB-beta degradation is not induced after sole partial hepatectomy.

CONCLUSION:

We propose that during liver regeneration, the transitory stimulation of the transcription factor response, assures blockade of NF-kappaB until recovery of the total mass of the liver and the persistent NF-kappaB activation in early hepatocarcinogenesis may be due to IkappaB-beta and IkappaB-alpha degradation, mainly IkappaB-beta degradation, which contributes to gene transcription related to proliferation required for neoplastic progression.

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