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

Rebeca Garcia-Roman, Julio Isael Perez-Carreon, Adriana Marquez-Quinones, Martha Estela Salcido-Neyoy, Saul Villa-Trevino
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, México D.F, Mexico
DOI: 10.1186/1477-3163-6-5

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-α 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 hepatocarconogenesis, the IkappaB-α degradation turned out to be acute and transitory, but the low levels of IkappaB-β persisted even 15 days after partial hepatectomy. Interestingly, IkappaB-β 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-β and IkappaB-α degradation, mainly IkappaB-β degradation, which contributes to gene transcription related to proliferation required for neoplasic progression.