INTERFERON-BETA INDUCES S-PHASE ACCUMULATION SELECTIVELY IN HUMAN TRANSFORMED-CELLS

Interferons (IFNs) generally have been characterized as antiproliferat ive cytokines, The cell cycle arrest in G(1)/G(0) phase induced by typ e I IFNs, especially IFN-alpha, was recognized as a manifestation of t heir antiproliferative effects, In this article, we report that the ce ll cycle block in G(1)/G(0) is observed mainly in certain cell types, such as Daudi Burkitt's lymphoma cells, In a variety of human transfor med cells, but not nontransformed primary cells, IFN-beta and IFN-alph a induced a significant increase in the S phase population, The increa se appeared to be due to a continued S phase entry and subsequently a failure of S phase cells to transit efficiently into G(2) and M phases , The ability of tumor cells to exhibit the S phase effect correlated with proper IPN signaling and loss or inactivation of the normal G(1) checkpoint conferred by the retinoblastoma protein (pRB). Overriding t he G(1) checkpoint switched human nontransformed primary cells from no nresponsive to sensitive to the IFN-induced effect. Therefore, the cel l cycle regulatory machinery could function, at least in part, as a de termining factor that affects the IFN-induced cell cycle effect, The I FN effect in transformed cells may suggest intriguing prospects for co mbinatorial therapies for cancer.