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Potential for the 2G Single Nucleotide Polymorphism in the Promoter of Matrix Metalloproteinase to Enhance Gene Expression in Normal Stromal Cells¹

Departments of Biochemistry [C. A. W., C. E. B.] and Medicine [C. I. C., C. E. B.], Dartmouth Medical School, Hanover, New Hampshire 03755, and the Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03766 [J. J. G.]

The 1G/2G polymorphism of matrix metalloproteinase 1 (MMP-1) affects activity of the promoter in transient transfections, and has been associated with the incidence orinvasiveness of five types of cancer. In light of these findings, and because stromal cells may contribute to tumor cell invasion, we used quantitative real-time reverse transcription-PCR to measure endogenous MMP-1 mRNA expression in 34 human foreskin fibroblasts homozygous or heterozygous for the 1G and 2G alleles. We measured basal, cytokine, and growth factor induced MMP-1 mRNA expression. The genotype of the MMP-1 promoter polymorphism was not predictive of mean MMP-1 mRNA expression. However, within the population of cell lines with at least one 2G polymorphism, there were more individuals with higher levels of MMP-1 mRNA after treatment with a cytokine or growth factors. Our data suggest that the presence of the 2G polymorphism does not significantly affect mean expression levels of a population but may increase the potential for an individual to have higher MMP-1 expression in response to growth factors and cytokines.

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