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

Fertil Steril. 2004 Sep;82(3):639-49. doi: 10.1016/j.fertnstert.2004.01.047.

Abstract

Objective: 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.

Design: Whole-genome analysis of mRNA levels in leiomyoma and normal myometrium tissue samples.

Setting: University research laboratory.

Patient(s): Eight patients of varying age and race undergoing surgery for symptomatic fibroids.

Intervention(s): After tissue collection of five tumors and five normals from human pathological specimens, labeled cRNA was generated and hybridized to the oligonucleotide-composed arrays.

Main outcome measure(s): Quantification of transcript expression levels in uterine fibroids relative to normal myometrium.

Result(s): Model-based expression analysis revealed that of the 22,500 transcripts represented on the arrays, 226 genes were found to be dysregulated by a > or =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.

Conclusion(s): 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • In Situ Hybridization
  • Leiomyoma / genetics*
  • Leiomyoma / pathology
  • Leiomyoma / surgery
  • Menstrual Cycle
  • Myometrium / pathology
  • Oligonucleotide Array Sequence Analysis / methods
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / pathology
  • Uterine Neoplasms / surgery