Activation of transcription factors NF-kappaB and AP-1 and their relations with apoptosis associated-proteins in hepatocellular carcinoma.

Aim: To study the distribution pattern of transcription factors NF-kappaB and AP-1 and their relations with the expression of apoptosis associated-proteins Fas/FasL and ICH-1L/S in human hepatocellular carcinoma (HCC).

Methods: We performed in situ hybridization and immunohistochemical techniques for NF-kappaB, AP-1, Fas/FasL and ICH-1 in 40 cases of human HCC along with corresponding nontumoral tissues and 7 cases of normal liver tissues.

Results: Twenty-two (55%) and 25 (62.5%) of 40 cases for NF-kappaB and AP-1 were presented for nuclear or both nuclear and cytoplastic staining respectively, while less cases were presented for only cytoplastic staining for NF-kappaB (18%) and AP-1 (10%) in adjacent nontumoral tissues and negative staining in normal liver tissues. There was no statistically significant difference of NF-kappaB or AP-1 activation between well differentiated tumors and poorly differentiated tumors (P>0.05). NF-kappaB activity is positively corresponded to AP-1 activation. The expression of ICH-1L/S was associated with the activation of NF-kappaB and AP-1 (P<0.05), but no significant relationship was found between Fas/FasL and NF-kappaB or AP-1(P>0.05).

Conclusion: Activation of both NF-kappaB and AP-1 may be required for ICH-1L/S-induced apoptosis in HCC, but not for Fas/FasL-mediated apoptosis. NF-kappaB and AP-1 may play important roles in the pathogenesis of human HCC.