DIFFERENTIAL EXPRESSION OF THE P27(KIP1) MESSENGER-RNA IN IFN-SENSITIVE AND RESISTANT CELL-LINES

IBNs arrest the growth of a small cell lung cancer (SCLC) cell line NC I-H82 in the G1 phase but not the growth of the derived cell line NCI- H82R. Progression through the G1 phase is controlled by positive and n egative regulatory genes. Oncoviral genes can override this control. I n this study, we compared the effects of human IFN alpha 2b on the mRN A levels of the Cdk inhibitor p27(Kip1) in NCI-H82, NCI-H82R and HPV 1 6 E7-transfected NCI-H82 cell lines. Induction of the 2-5 Oligoadenyla te synthetase (2-5 GAS) gene was used as a marker of IFN-dependent sig nal transduction The expression of p27(Kip1) mRNA increased at 48 and 72 hr after IFN alpha 2b addition in sensitive cells. In contrast, p27 (Kip1)mRNA had only slight variations in both the resistant and E7-tra nsfected cells. Interestingly, the E7-transfected NCI-H82 cells became resistant to the IFN alpha 2b anti-proliferative effect. Our results suggest that p27(Kip1) could be a key mediator of the IFN alpha 2b-ind uced growth arrest and that HPV 16 E7 might affect p27(Kip1) inducibil ity, originating IFN alpha ab-resistant cells. (C) 1998 Academic Press .