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Gene Expression Profile of Leiomyoma and Myometrium and the Effect of Gonadotropin Releasing Hormone Analogue Therapy

Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida; Department of OB/GYN, University of Florida, Box 100294, Gainesville FL 32610; cheginin{at}obgyn.ufl.edu

Juan Verala, BS

Xiaoping Luo, MD

Jingxia Xu, MS

R. Stan Williams, MD

Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida

Objective: To determine the profile of differentially expressed genes in leiomyoma and matched unaffected myometrium and to identify the genes whose expression are altered after gonadotropin releasing hormone analogue (GnRHa) therapy.

Methods: Using total RNA isolated from untreated and GnRHa-treated leiomyoma and myometrium subjected to Clontech Atlas 1.2 K cancer microarray containing 1176 known genes, we found transcripts for many cytokines, growth factors and their receptors, adhesion molecules, extracellular matrix, proteases, signaling intermediates, and transcription factors in both tissues. Based on the overall normalization and reproducibility of the results, 328 differentially expressed and regulated genes with at least threefold change in their expression in untreated and GnRHa-treated tissues were chosen for further analysis.

Results: The expression value of the 328 genes subjected to significance analysis of microarray showed a total of 100 genes with relative significant change in expression. Of these genes, the expression of 18 was up-regulated and 82 down-regulated in untreated leiomyoma compared with myometrium. In GnRHa-treated tissues, the expression of 34 genes showed a significant decrease in leiomyoma, whereas 27 genes increased and 15 decreased in myometrium compared with their respective untreated tissues. There was no difference in the expressive profile of these genes when comparing leiomyoma and myometrium from the GnRHa-treated group. Hierarchical duster analysis revealed that these differentially expressed or regulated genes, classified based on their biologic functions, are involved in regulation of cell growth/cycle, signal transduction, transcription factors, and cell and tissue structure.

Conclusion: Microarray analysis allowed us to identify the profile expression of several specific genes in leiomyoma and myometrium whose expression appears to be differentially regulated after GnRHa therapy.

Key Words: Leiomyoma • myometrium • gonadotropin releasing hormone analogue • gene profiling

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