An Upstream Estrogen Response Element Linked to Exogenous p53 Tumor Suppressor Gene Expression Differentiates Effects of the Codon 72 Polymorphism

The objective of this study was to assess the effects of an upstream estrogen response element (ERE)on exogenous p53 tumor suppressor gene with a codon 72 polymorphism about which there have beencontroversial reports in relation to cancer risk. The p53 gene (bases 166–1143 from start codon) with the codon72 polymorphism, inserted into the pIRES-hrGFP II plasmid with or without upstream ERE, were transfectedinto HHUA endometrial cancer cells expressing the estrogen receptor. The ERE-linked p53 gene with the prolinevariant at codon 72 showed lower transfection rates than the gene without ERE or with the arginine variantat codon 72. p21 expression was significantly higher in HHUA cells transfected with the proline variant genethan in those transfected with the arginine variant gene. We consider that the presence of an upstream EREpromotes the transcriptional effects of the exogenous p53 gene with the proline variant, which strengthens theexpression of p21, and results in lower transfection rates through cell cycle inhibition.