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Activation of the IGF-II Gene by HBV-X Protein Requires PKC and p44/p42 Map Kinase Signalings

2001; Elsevier BV; Volume: 283; Issue: 2 Linguagem: Inglês

10.1006/bbrc.2001.4767

1090-2104

Sukmi Kang-Park, Je‐Ho Lee, Jeh-Hoon Shin, Young Ik Lee,

Metabolism, Diabetes, and Cancer

We have recently shown that HBx protein, one of the causative agents of hepatocellular carcinomas, regulates Sp1 mediated transcription of insulin-like growth factor II promoter 4 (Lee et al. (1998) Oncogene 16, 2367–2380). Here we show that PKC and p44/p42MAPK signalings are required for the HBx-induced Sp1-mediated IGF-II P4 transcriptional activity since (i) PKC activation by PMA or PKC expression vector increases Sp1 phosphorylation and P4 activity in HBx-transfected HepG2 cells; (ii) PKC inhibition by PKC inhibitor Gö6976 reduces Sp1 phosphorylation, P4 activity, and IGF-II mRNA in HBx-transfected HepG2 cells; and (iii) the inhibition of MEK activation by U0126 reduces Sp1 phosphorylation, P4 activity and IGF-II mRNA in HBx-transfected HepG2 cells. These results demonstrate that PKC and p44/p42 MAPK cascades are the essential signaling pathways in Sp1-mediated IGF-II gene activation by HBx.