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8 STUDY OF DIFFERENTIALLY EXPRESSED GENES IN LEIOMYOMATA AS COMPARED TO NORMAL MYOMETRIUM.
  1. T. Medina,
  2. J. Richer,
  3. K. Horwitz
  1. University of Colorado at Denver and Health Sciences Center, Aurora, CO

Abstract

Uterine leiomyomata (or fibroids) are a benign tumor of smooth muscle cell origin with extensive deposition of extracellular matrix proteins. Uterine leiomyomata are extremely common among women of reproductive age and may cause abnormal menstrual bleeding, pelvic pain, and/or infertility. Uterine leiomyomata are known to be under control of ovarian hormones. This study confirmed the expression of seven genes by RT-PCR, Mst4, EFEMP1, MMP-11, MMP-7, MMP-28, RNF28, DSG2, which were found to be disregulated in a microarray analysis. EFEMP1, MMP-11, MMP-7, MMP-28, and DSG2 have all been shown to be under the influence of ovarian hormones. The RT-PCR was performed on 13 uterine leiomyomata paired with 11 normal myometrium from 5 patients. There was some variability but most of the patient samples showed a decrease in mRNA expression for Mst4, EFEMP1, and MMP-7 in the uterine leiomyomata (as expected). Similarly, many of the patient samples also confirmed the increase in mRNA expression of MMP-11 and DSG2 in the leiomyomata (as expected). RNF28 and MMP-28 showed the greatest variability between the patient samples. Immunohistochemistry was used to examine the protein expression for MMP-11 and Mst4. The MMP-11 protein was in concordance with the mRNA for MMP-11, both increased in most of the uterine leiomyomata samples. However, the Mst4 protein expression was increased in the uterine leiomyomata while the mRNA was decreased. Further research should be done to determine how disregulation (either over or underexpression) of these genes contributes to the etiology of this disease and what role the ovarian hormones play in its development. It may be possible in the future to target one or more of these genes or their protein products as a nonsurgical treatment of uterine leiomyomata.

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