Molecular Human Reproduction, Vol. 9, No. 9, 541-549,
September 2003
© 2003 European Society of Human Reproduction and Embryology
Article |
Fibroids display an anti-angiogenic gene expression profile when compared with adjacent myometrium
Submitted on March 17, 2003; resubmitted on April 2, 2003. accepted on April 8, 2003
1 Centre for Women’s Health Research, Monash University Department of Obstetrics & Gynaecology, 246 Clayton Rd., Melbourne, 2 Victorian Bioinformatics Consortium, Monash University, Melbourne and 3 CSIRO, Mathematical and Information Sciences, Melbourne, Australia
4 To whom correspondence should be addressed. e-mail: gareth.weston{at}med.monash.edu.au
The aetiology of uterine fibroids remains unknown, despite causing significant gynaecological morbidity. Fibroids have a reduced microvascular density when compared with adjacent myometrial tissue. The aim of this study was to identify genes with differential expression between fibroid and adjacent normal myometrium, particularly genes with a role in angiogenesis. Total RNA was extracted from fibroid/myometrium pairs from 12 hysterectomy specimens, and used to perform 24 cDNA microarrays. There were 10 500 genes screened on each microarray for differential expression. Analysis of expression data was carried out using multiple t-tests, as well as a novel class prediction algorithm (GeneRaVETM). The differential gene expression of selected genes was confirmed by quantitative ‘real time’ RT–PCR. Selected genes with a role in angiogenesis were further analysed for expression in isolated cell populations of endothelial cells (fibroid and myometrium) and smooth muscle cells (fibroid and myometrium), to see if their expression was confined to particular cell types. Twenty-five genes with differential gene expression between fibroid and myometrium were identified. Insulin-like growth factor-2, endothelin A receptor, connective tissue growth factor (CTGF), cysteine-rich angiogenic inducer 61 (CYR61) and collagen 4
2 (COL4A2) were confirmed by RT–PCR. CTGF and CYR61, both angiogenesis promoters, were reduced in expression relative to myometrium. COL4A2, the precursor for an angiogenesis inhibitor, canstatin, was increased relative to myometrium. These three genes display an anti-angiogenic expression profile in fibroids relative to myometrium. These findings may explain the reduced microvascular density seen in fibroids relative to myometrium.
Key words: angiogenesis/COL4A2/CTGF/CYR61/fibroid/microarray
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