Gene Expression Profiles of Uterine Normal Myometrium and Leiomyoma and Their Estrogen Responsiveness In Vitro.
- Author:
Eun Ju LEE
1
;
Prati BAJRACHARYA
;
Dong Mok LEE
;
Kyung Hyun CHO
;
Keuk Jun KIM
;
Young Kyung BAE
;
Mi Jin KIM
;
Ki Ho LEE
;
Hang Jin KIM
;
Gun Ho SONG
;
Sang Sik CHUN
;
Inho CHOI
Author Information
1. Department of Biotechnology, College of Medicine, Yeungnam University, Gyeongsan, Korea. inhochoi@ynu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Leiomyoma;
17beta-estradiol;
Uterus;
Oligonucleotide array sequence analysis;
Immunohistochemistry
- MeSH:
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
- From:Korean Journal of Pathology
2010;44(3):272-283
- CountryRepublic of Korea
- Language:English
-
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.