Steroid-mediated inhibition of radiation-induced apoptosis in C4-1 cervical carcinoma cells is p53-dependent

In human papillomavirus (HPV) infected cervical epithelial cells the synthe tic steroid dexamethasone inhibits radiation-induced apoptosis and increase s the transcription of HPV E6/E7, enhancing p53 degradation. The aim Of thi s Study was to determine if suppression of apoptosis was mechanistically li nked to changes in p53. HPV 16 E6 or E6/E7 expression vectors were transien tly transfected into C4-1 HPV 18-positive cervical carcinoma cells to mimic the enhanced transcription following steroid treatment. After irradiation, apoptosis was suppressed in these cells comparable to the effect observed after steroid treatment alone. To confirm whether loss of p53 was responsib le for the inhibition of apoptosis, residual p53 in C4-1 cells was targeted by stable transfection with a dominant-negative p53 mutant. While radiatio n-induced apoptosis increased after Mutant transfection, inhibition of prog rammed cell death by steroid treatment was either eliminated or substantial ly reduced. Steroid-dependent inhibition of radiation-induced apoptosis in carcinoma of the cervix involves E6 modulation or p53 expression and may ad versely affect treatment. (C) 2001 Elsevier Science Ltd. All rights reserve d.