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

Abstract

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 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.

FIGURE 1

Patient information and location of uterine tissues collected at the follicular or luteal phase of the menstrual cycle (Wt = white; Blk = black; Hisp = Hispanic). In this uterine cross-section diagram, leiomyoma and myometrial samples are shown by an arch and a rectangle, respectively.