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Involvement of nuclear receptor coactivator SRC-1 in estrogen-dependent cell growth of MCF-7 cells
1Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, 412-8513, Japan.
Abstract:
Steroid hormones regulate cell growth and function through the transcriptional control of target genes by their cognate nuclear receptors. These receptors bind to ligands and associate with transcriptional cofactors to stimulate transcription. SRC-1, one of the nuclear receptor coactivators, is known to interact with nuclear receptors and enhance transactivation function in a ligand-dependent manner. In this study, to assess the function of SRC-1 in cell growth regulated by nuclear receptor ligands, we established a stable transformant cell line overexpressing human SRC-1 and studied the action of 17beta-estradiol (E(2)) on cell growth as well as the expression of E(2)-responsive genes in MCF-7 cells. We found that SRC-1 overexpression potentiates cell growth stimulated by E(2) in accordance with enhancement of transcriptional activation of exogenous and endogenous E(2)-responsive genes. These findings clearly indicate the importance of nuclear receptor coactivators for the activities of steroid/lipophilic vitamins in cell growth and gene expression.
Insights
Steroid receptor coactivator 1 (SRC-1) enhances cell growth and gene expression. Overexpressing SRC-1 boosts responses to 17beta-estradiol (E(2)) in MCF-7 cells, highlighting coactivator importance.
Area of Science:
- Molecular Endocrinology
- Cellular Biology
- Gene Regulation
Background:
- Steroid hormones regulate cell growth and function via nuclear receptors controlling target gene transcription.
- Nuclear receptors bind ligands and recruit coactivators, such as Steroid Receptor Coactivator-1 (SRC-1), to enhance gene transcription.
- SRC-1 is known to interact with nuclear receptors and potentiate their transactivation function in a ligand-dependent manner.
Purpose of the Study:
- To investigate the role of SRC-1 in mediating cell growth and gene expression regulated by nuclear receptor ligands.
- To assess the impact of SRC-1 overexpression on 17beta-estradiol (E(2))-induced cellular responses in MCF-7 cells.
Main Methods:
- Established a stable MCF-7 cell line overexpressing human SRC-1.
- Studied the effects of 17beta-estradiol (E(2)) on cell growth in SRC-1 overexpressing cells.
- Analyzed the expression of E(2)-responsive genes in response to SRC-1 overexpression and E(2) treatment.
Main Results:
- SRC-1 overexpression significantly potentiated E(2)-stimulated cell growth in MCF-7 cells.
- Enhanced transcriptional activation of both exogenous and endogenous E(2)-responsive genes was observed.
- The results demonstrate a direct correlation between SRC-1 levels and E(2)-mediated cellular proliferation and gene expression.
Conclusions:
- Nuclear receptor coactivators, exemplified by SRC-1, are crucial for mediating the effects of steroid hormones on cell growth.
- SRC-1 plays a significant role in amplifying ligand-dependent transcriptional activity of nuclear receptors.
- These findings underscore the importance of coactivators in steroid hormone signaling pathways regulating cellular processes and gene expression.