Gene Expression Profiles of Uterine Normal Myometrium and Leiomyoma and Their Estrogen ResponsivenessIn Vitro
Abstract
Background : Uterine leiomyomas are common benign smooth muscle tumors among the reproductive aged-women.The research has been aimed to identify the differentially expressed genes between normal myometrium and leiomyoma and to investigate the effects of E2 on their expression.Methods : Gene microarray analysis was performed to identify the differentially expressed genes between normal myomerium and leiomyoma.The data was confirmed at protein level by tissue microarray.Results : Gene microarray analysis revealed 792 upregulated genes in leiomyoma.Four genes (tropomyosin 4 [TPM4], collagen, type IV, alpha 2 [COL4a2], insulin-like growth factor binding protein 5 [IGFBP5 ] , tripartite motif-containing 28 [TRIM28]) showed the most dramatic upregulation in all leiomyoma samples.Tissue microarray analyses of 262 sample pairs showed significantly elevated expression of TPM4, IGFBP5, estrogen receptor-a, and progesterone receptor (PR) protein in leiomyoma from the patients in their forties, COL4a2 in the forties and fifties age-groups, and TRIM28 in the thirties age-group.PR, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R) and IGFBP5 were induced by E2 in in vitro culture of tissue explants from which cells migrated throughout the plate.Among these, PR, IGF-1, IGFBP5 genes showed higher expression in tissue compared to cells-derived from tissue in leiomyoma and IGF-1R in leiomyoma cell.Conclusions : This observation implies the importance of the whole tissue context…
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