Expression pattern of AP-2 transcription factors in cervical cancer cells and analysis of their influence on human papillomavirus oncogene transcription

The AP-2 family of transcription factors consists of three known members, n amely AP-2 alpha, AP-2 beta, and AP-2 gamma In experimental systems AP-2 fa ctors, possess tumor suppressor-like activities, and alterations in the AP- 2 expression pattern have been described for some tumor entities. In additi on, AP-2 has been implicated in the transcriptional control of human papill omaviruses (HPVs). We investigated here the expression pattern of AP-2 alph a, AP-2 beta, and AP-2 gamma, as well as that of the cellular AP-2 target g ene c-erbB-2, in a series of cervical cancer cell lines. In addition, we an alyzed the influence of AP-2 factors on the activity of the HPV16 and HPV18 E6/E7 oncogene promoter. We found that, with the exception of HPV-negative C33A cells, all investigated cervical cancer cell lines expressed all thre e AP-2 family members, although at varying levels. No linear correlation be tween AP-2 and c-erbB-2 levels was observed. Although AP-2 alpha, AP-2 beta , and AP-2 gamma can activate the c-erbB-2 promoter in reporter gene assays , they do not stimulate the HPV 16 or HPV 18 E6/E7 promoter. These results indicate that, although a rare event, loss of AP-2 expression occurs in cer vical cancer cells. Moreover, AP-2 alpha., AP-2 beta, and AP-2 gamma are ne ither sufficient nor required to activate the viral E6/E7 promoter.