P53 tumour suppressor modulates transcription of the TATA-less gene codingfor the tumour-associated carbonic anhydrase MN/CA IX in MaTu cells

MN/CA IX (MN) exhibits a strong association with tumours. Co-transfection e xperiments revealed that in MaTu cells the activity of the (-173;+31) MN pr omoter construct was repressed by the wild type p53 in a dose-responsive ma nner and stimulated by the (143(Val-Ala)) mutant. Upregulation of endogenou s p53 by mitomycin C treatment in MaTu cells also had a profound effect on MN expression as well as the activity of MN promoter in a reporter construc t, p53 can thus modulate MN expression and at least in a subset of tumours the changed p53 status might be responsible for MN positivity. Co-transfect ions with internally deleted MN promoter constructs demonstrated that the w ild type p53 exerts its repression activity on the level of the basal trans criptional machinery and not on a particular cis element within the MN prom oter. (C) 2000 Elsevier Science B.V. All rights reserved.