¹Dipartimento di Biochimica e Biofisica 'F. Cedrangolo', Il Università di Napoli, Italy

²Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università 'Federico II' di Napoli, Italy

³Istituto Nazionale Tumori, Fondazione 'G. Pascale', Napoli, Italy

Correspondence to: Alberto Abbruzzese, Dipartimento di Biochimica e Biofisica 'F. Cedrangolo', Il Università di Napoli, via Costantinopoli, 16 80138 Napoli, Italy tel: +39 81 5665871; fax: +39 81 5665863; e-mail: abbruzze@cds.unina.it

^aCurrent address: Dipartimento di Medicina Sperimentale e Clinica, Università 'Magna Graecia', Catanzaro, Italy

Edited by S. Martin

We have demonstrated that interferon-2-recombinant (IFN) at growth inhibitory concentrations enhances the expression and signalling activity of the epidermal growth factor receptor (EGF-R) in human epidermoid carcinoma KB cells. Here we report that KB cells exposed to IFN underwent apoptotic cell death and this effect was antagonized by EGF. We have also found that IFN enhanced the expression of heat shock proteins (HSP) HSP-70, HSP-90 and HSP-27 and activated the NH₂-terminal Jun kinase-1 (JNK-1) and p38 mitogen activated protein kinase, the target enzymes of a stress-dependent intracellular transduction pathway. Moreover, the overexpression of the wild-type JNK-1, obtained through plasmid transfection of KB cells, induced apoptosis which was potentiated by the exposure of wild-type JNK-1 (JNK-1^wt)-transfected cells to IFN. All these effects were neutralized by the addition of EGF to parental and JNK-1^wt-transfected KB cells exposed to IFN. In conclusion, EGF has a protective effect on KB cells from apoptosis while antagonizing a stress response elicited by IFN and targeted on the stress pathway terminal kinases.

Interferon-; epidermal growth factor; tumour cells; apoptosis; JNK-1; heat shock proteins