Interferons (IFNs) are cytokines that are involved in the regulation of diverse cellular functions, including modulation of immune responses, inhibition of proliferation, and induction of resistance to viral and bacterial infection (Gutterman, 1994). IFNs employ a unique signalling pathway for rapid induction of gene expression by utilizing two groups of critical elements to transduce the signals from cell surface receptor to nuclear events. The first is the janus family kinases (JAKs), a group of tyrosine kinases containing JAK1, JAK2, JAK3 and TYK2, and the second is STAT (signal transducers and activators of transcription) proteins, a group of latent cytoplasmic transcription factors which are activated by phosphorylation (Darnell, 1997;Pellegrini and Dusanter-Fourt, 1997). Upon IFN stimulation, receptor-associated JAKs are phosphorylated and activated and these kinases, in turn, phosphorylate and activate STAT proteins which then translocate from cytoplasm to nucleus and direct transcriptional activation of various effector genes. The essential role of JAKs and STATs in IFN signalling pathway has been demonstrated by the IFN-resistant phenotypes of cells lacking the JAK or STAT gene products (Muller et al, 1993;Xu et al, 1994).Recent studies have shown that IFNs are the most promising anti-viral agents for the treatment of patients with chronic hepatitis B. These cytokines have been reported to suppress hepatitis B virus (HBV) enhancer activity, reduce virus replication and activate hepatocellular gene expression in cultured liver cells (Tur-Kaspa et al, 1990;Zhang and McLachlan, 1994). Additionally, results from clinical trials also demonstrated that IFNs caused inhibition of HBV replication and reduction of hepatitis B surface antigen (HBsAg) expression (Alexander et al, 1987;Korenman et al, 1991). These studies suggest that IFNs are useful anti-viral drugs for the treatment of patients with viral hepatitis. However, the use of IFNs in the therapy of liver cancer seems discouraging. Although several studies have shown that IFNs exerted growth-inhibitory effects on human hepatoma cells (Lai et al, 1989;Boue et al, 1990), other works showed that patients with advanced hepatocellular carcinoma were resistant to IFNs (Nair et al, 1985;Sachs et al, 1985). However, the molecular basis of this resistance is not clear.Recent studies have indicated that the responses of cells to IFNs could be modulated by regulating the expression or the activity of JAKs and STATs. It has been found that elevated activity of JAKs enhanced the anti-tumour effects of IFNs to lymphoblastoid cells (Lee et al, 1997). Similarly, induction of STATs gene expression by retinoic acids in IFN-unresponsive breast cancer cells and myeloid leukaemia cells permitted growth inhibition by IFNs (Kolla et al, 1996;Weihua et al, 1997). These data suggest that the resistance of cancer cells to IFNs may be due to a relative deficiency of IFN signalling molecules and argue that overexpression of these signalling molecules may restore the responsiveness o...

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