Calcium Regulates the Differentiation of Vitamin A-Responsive Human Papillomavirus-Immortalized Cervical Keratinocytes, But Not the Expression of the Papillomavirus E6 and E7 Oncogenes

Abstract

Transcription of the papillomavirus virus open reading frame encoding oncogenes E6 and E7 is necessary for cell immortalization and is known to be regulated as a function of cell differentiation in cervical tumors in vivo. Thus, it is important to understand how exogenous factors regulate transcription from the HPV P₉₇ promoter. Vitamin A and other retinoids are important dietary agents that regulate normal ectocervical epithelial cell differentiation. Moreover, these agents have also been shown to be clinically useful in reducing the mass of cervical tumors. In a previous study supported by the AICR, we examined the effects of vitamin A and other retinoids on the differentiation of an HPV16-immortalized cervical cell line, ECE16-1. We showed that HPV16-immortalization sensitizes HPV16 transformed cells to the effects of retinoids [Agarwal et al., Cancer Res 51: 3982–3989 (1991)].