Korean J Pathol.  2010 Jun;44(3):272-283.

Gene Expression Profiles of Uterine Normal Myometrium and Leiomyoma and Their Estrogen Responsiveness In Vitro

• Lee EJ
• Bajracharya P
• Lee DM
• Cho KH
• Kim KJ
• Bae YK
• Kim MJ
• Lee KH
• Kim HJ
• Song GH
• Chun SS
• Choi I

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 [COL4alpha2], 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-alpha, and progesterone receptor (PR) protein in leiomyoma from the patients in their forties, COL4alpha2 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 including the cells-derived from tissue in the research for the understanding of molecular mechanism of leiomyoma. Here, we report higher expression of TRIM28 in leiomyoma for the first time and identify E2-responsive genes that may have important roles in leiomyoma development.

Keyword

Leiomyoma; 17beta-estradiol; Uterus; Oligonucleotide array sequence analysis; Immunohistochemistry

MeSH Terms

Animals
Collagen Type IV
Estrogens
Female
Gene Expression
Humans
Immunohistochemistry
Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor I
Leiomyoma
Mice
Microarray Analysis
Myometrium
Oligonucleotide Array Sequence Analysis
Receptor, IGF Type 1
Receptors, Progesterone
Smooth Muscle Tumor
Tissue Array Analysis
Transcriptome
Up-Regulation
Uterus
Collagen Type IV
Estrogens
Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor I
Receptor, IGF Type 1
Receptors, Progesterone