Insights from gene arrays on the development and growth regulation of uterine leiomyomata.

ObjectiveTo use microarray analysis as an unbiased approach to identify genes involved in the induction and growth of uterine leiomyomata.DesignScreen by arrays for up to 12,000 genes in leiomyoma (L) and control myometrium (M) from nine patients.SettingUniversity research laboratories.Patient(s)Nine patients in the follicular and luteal phases of the menstrual cycle.Intervention(s)mRNA from L and M was converted to biotin-labeled cRNA and hybridized to cDNA oligonucleotide sequences on the arrays.Main outcome measure(s)Greater than two-fold change in gene expression between leiomyoma and matched myometrium.Result(s)Prominent among the 67 genes overexpressed in L relative to M were dlk or Pref-1, doublecortin, JM27, ionotropic glutamate receptor subunit 2, apolipoprotein E3, IGF2, semaphorin F, myelin proteolipid protein, MEST, frizzled, CRABP II, stromelysin-3, and TGFbeta3. The genes dlk, IGF2, and MEST are paternally expressed imprinted genes, and the others are involved in tissue differentiation and growth. Prominent among the 78 genes down-regulated in L relative to M were alcohol dehydrogenases 1alpha-gamma, tryptase, dermatopontin, thrombospondin, coxsackievirus receptor, nur77, and c-kit.Conclusion(s)Arrays offer large-scale screening of mRNA expression, which will help us differentiate between the genes and metabolic pathways necessary for leiomyoma growth and those regulating myometrial contractions.