Molecular characterization of uterine fibroids and its implication for underlying mechanisms of pathogenesis

Paul J. Hoffman, Dawn B. Milliken, Laurie C. Gregg, Ryan R. Davis, Jeffrey Gregg

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

To identify genes involved in fibroid development by performing global expression profiling on tissues of normal myometrium and uterine leiomyoma origin using Affymetrix HG-U133A GeneChip® microarrays. Whole-genome analysis of mRNA levels in leiomyoma and normal myometrium tissue samples. University research laboratory. Eight patients of varying age and race undergoing surgery for symptomatic fibroids. After tissue collection of five tumors and five normals from human pathological specimens, labeled cRNA was generated and hybridized to the oligonucleotide-composed arrays. Quantification of transcript expression levels in uterine fibroids relative to normal myometrium. Model-based expression analysis revealed that of the 22,500 transcripts represented on the arrays, 226 genes were found to be dysregulated by a ≥1.5-fold change between leiomyoma and normal myometrium. Moreover, our research identified many dysregulated apoptosis-related genes, of particular interest was TRAIL and Ask1, and also found numerous differentially expressed proliferation genes, including TGFB1, PDGFC, and two dual specificity phosphatases. These results indicate that these genes may play a significant role in the development of leiomyomas from normal uterine tissue. We hypothesize that the deregulation of apoptotic and proliferative processes is pivotal to fibroid development.

Original languageEnglish (US)
Pages (from-to)639-649
Number of pages11
JournalFertility and Sterility
Volume82
Issue number3
DOIs
StatePublished - Sep 2004

Keywords

  • Affymetrix
  • apoptosis'
  • gene expression
  • Leiomyoma
  • microarray
  • myometrium

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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