2010. Vol. 52, N 12, p. 977–982
INTERFERON γ-MEDIATED GROWTH REGULATION OF EPITELIAL CELLS

E. B. Burova,1 I. S. Smirnova, A. N. Shatrova, I. V. Gonchar, N. N. Nikolsky

Institute of Cytology RAS, St. Petersburg;
1 e-mail: lenbur87@mail.ru

Interferon gamma (IFNγ) is known to inhibit proliferation of certain transformed cell lines. Recently, we have demonstrated the transactivation of the epidermal growth factor receptor (EGFR) in response to IFNγ (Burova et al., 2007) and provided direct evidence for the dependence of IFNγ-induced EGFR transactivation upon EGFR expression level in epithelial cells (Gonchar et al., 2008). This study examines an antiproliferative effect of IFNγ on human epithelial cells lines A431 and HeLa which express high levels of EGFR, as well as HEK293, which expresses low levels of EGFR. We characterized the IFNγ-induced changes in these cells by studying cell growth, the cell cycle and induction of apoptosis. The response to IFNγ differed in the tested cell lines: cell growth was inhibited in both A431 and HeLa cells, but not in HEK293 cells, as shown by cell counts and MTT. The cell cycle phases analyzed by flow cytometry were disturbed in A431 and HeLa cells in response to IFNγ. In contrast, IFNã treatment did not alter distribution by cell cycle phases in HEK293. Our results indicate that IFNγ exhibit an antiproliferative effect depending on the increased expression of EGFR in A431 and HeLa cells. Further, it was demonstrated that IFNγ induced the caspase 3 activation in A431 cells, suggesting an involvement of active caspase 3 in IFNγ-induced apoptosis.

Key words:  IFNγ, epidermal growth factor receptor, apoptosis, cell cycle, A431, HeLa


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