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Updated: Oct 2, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Activation of antimetastatic Nm23-H1 gene expression by estrogen and its alpha-receptor
Kwang-Huei Lin1, Won-Jing Wang, Yi-Hsin Wu
1Department of Biochemistry, Chang-Gung University, Taoyuan, Taiwan, Republic of China. khlin@mail2000.com.tw
Abstract:
Metastasis of various malignant cells is inversely related to the abundance of the Nm23-H1 protein. The role of estrogens in tumor metastasis has now been investigated by examining the effect of E2 on the expression of the Nm23-H1 gene. Three human breast carcinoma cell lines, in which endogenous ERalpha is expressed at different levels, were used as a tool to assess the role of ERalpha in Nm23-H1 gene-mediated metastasis. E2 induced time-dependent increases in the abundance of Nm23-H1 mRNA and protein, with the extent of these effects correlating with the level of expression of ERalpha. E2 induced a marked decrease in the invasive activity of MCF-7 and BT-474 cells but had no effect on BCM-1 cells, which had virtually no ERalpha. Consistent with these results, the ER-mediated Nm23-H1 promoter activity was inhibited 3-fold by the E2 antagonist, ICI 182,780. Deletion analysis of the promoter region of the Nm23-H1 gene identified a positive estrogen-responsive element located in -108/-94. ER protein bound specifically to the -108/-79 fragment with high avidity. These results indicate that E2, acting through ERalpha, activated transcription of the Nm23-H1 gene via a positive estrogen-responsive element in the promoter region of the gene. These results suggest that E2 could suppress tumor metastasis by activating the expression of the Nm23-H1 gene.
Insights
Estrogen (E2) activates the Nm23-H1 gene, increasing Nm23-H1 protein levels. This estrogen-driven Nm23-H1 expression suppresses breast cancer metastasis by reducing tumor cell invasiveness.
Area of Science:
- Molecular Biology
- Cancer Research
- Endocrinology
Background:
- Nm23-H1 protein abundance inversely correlates with malignant cell metastasis.
- Estrogen's role in tumor metastasis requires further investigation.
- Estrogen receptor alpha (ERalpha) expression varies across breast cancer cell lines.
Purpose of the Study:
- To investigate the effect of 17beta-estradiol (E2) on Nm23-H1 gene expression.
- To determine the role of ERalpha in E2-mediated regulation of Nm23-H1.
- To assess the impact of E2 on breast carcinoma cell invasive activity.
Main Methods:
- Utilized three human breast carcinoma cell lines with differing ERalpha expression levels.
- Measured Nm23-H1 mRNA and protein abundance following E2 treatment.
- Assessed cell invasive activity and Nm23-H1 promoter activity.
- Performed deletion analysis of the Nm23-H1 promoter region.
Main Results:
- E2 induced time-dependent increases in Nm23-H1 mRNA and protein, correlating with ERalpha levels.
- E2 significantly decreased the invasive activity of MCF-7 and BT-474 cells (high ERalpha), but not BCM-1 cells (low ERalpha).
- An estrogen-responsive element (ERE) at -108/-94 in the Nm23-H1 promoter was identified, where ER protein bound specifically.
Conclusions:
- E2, via ERalpha, activates Nm23-H1 gene transcription through a positive ERE in its promoter.
- E2-induced Nm23-H1 expression may suppress tumor metastasis.
- Nm23-H1 represents a potential therapeutic target for reducing breast cancer metastasis.
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