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

Objective: To use microarray analysis as an unbiased approach to identify genes involved in the induction and growth of uterine leiomyomata. Design: Screen by arrays for up to 12,000 genes in leiomyoma (L) and control myometrium (M) from nine patients. Setting: University 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 TGFβ3. 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 1α-γ, 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.