A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription

Matrix metalloproteinases (MMPs) facilitate cellular invasion by degrading the extracellular matrix, and their regulation is partially dependent on tr anscription. Binding sites for members of the Ets family of transcription f actors are present within MMP promoters and are potent positive regulators. We report a single nucleotide polymorphism at -1607 bp in the MMP-1 promot er, where an additional guanine (G) creates an Ets binding site, 5'-GGA-3'. This polymorphism displays significantly higher transcription in normal fi broblasts and in melanoma cells than the 1 G polymorphism, and it binds sub stantially more nuclear extract and recombinant ETS-1, Analysis of control DNAs from the Center d'Etude du Polymorphisme Humain pedigrees reveals that this polymorphism is not a mutation, with a frequency of the 2 G polymorph ism at 30%, In contrast, in eight tumor cell Lines, this frequency increase d to 62.5% (P < 0.0001). Thus, this MMP-1 polymorphism contributes to incre ased transcription, and cells expressing the 2 G polymorphism may provide a mechanism for more aggressive matrix degradation, thereby facilitating can cer progression.