Heterogeneous cross-talk of E2F family members is crucially involved in growth modulatory effects of interferon-gamma and EGF

Abstract

There is growing evidence that deregulation of E2F transcription factors is causatively involved in the patho-physiology of various tumors. However, no data on the role of E2F family members in tumor biology of ovarian cancer are available. We here describe an expression study of all known E2F transcription factors and their coactivators DP-1 and DP-2 in various human ovarian cancer cell lines and the breast cancer cell line T47D and their involvement in pathways affected by interferon-gamma and EGF. A significant overexpression of the proliferation-promoting E2F1 and especially E2F2 points to a pivotal role in modulating the uncontrolled proliferation in ovarian cancer cells. Of special note is the fact that interferon-gamma treatment did not only caused a reduction of the proliferation-promoting transcription factors E2F1 and E2F2, but also increased the inhibiting transcription factors E2F4 and E2F5, thus underlining the importance of an E2F cross-talk in the anti-proliferative function of interferon-gamma. Moreover, an increase in DP-1 and E2F3 is probably involved in the proliferation-enhancing effect of EGF. Our study provides a new insight in the crucial role of E2F cross-talk, especially the role of the inhibiting transcription factors E2F4 and E2F5, in the tumor biology of cancer and its possible usefulness as targets in anti-cancer therapy.