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

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.

• Authors: Paul J Hoffman, Dawn B Milliken, Laurie C Gregg, Ryan R Davis, Jeffrey P Gregg
• Journal: Fertility and sterility (Fertil Steril) Vol. 82 Issue 3 Pg. 639-49 (Sep 2004) ISSN: 0015-0282 [Print] United States
• PMID: 15374708 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Topics

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