scholarly journals Unique Roles of p160 Coactivators for Regulation of Breast Cancer Cell Proliferation and Estrogen Receptor-α Transcriptional Activity

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1588-1596 ◽  
Author(s):  
Sudipan Karmakar ◽  
Estrella A. Foster ◽  
Carolyn L. Smith
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Small Interfering Rna ◽  
Breast Cancer Cells ◽  
Transcriptional Activity ◽  
Interfering Rna ◽  
Mcf 7

Each of the three members of the p160 steroid receptor coactivator (SRC) family of coactivators (SRC-1, SRC-2 and SRC-3) stimulates estrogen receptor (ER)-α function in trans-activation assays. Consequently, we sought to elucidate their contributions to the ER-regulated processes of cell proliferation, apoptosis, and the expression of ERα target genes in MCF-7 breast cancer cells. The small interfering RNA depletion of SRC-2 or SRC-3 but not SRC-1 inhibited growth of MCF-7 cells, and this was reflected in decreased cell cycle progression and increased apoptosis in SRC-2- or SRC-3-depleted cells as well as a reduction in ERα transcriptional activity measured on a synthetic reporter gene. However, only SRC-3 depletion blocked estradiol stimulated cell proliferation. Depletion of SRC-1 did not affect these events, and together this reveals functional differences between each of the three SRC family coactivators. Regulation of the endogenous ERα target gene, c-myc was not affected by depletion of any of the p160 coactivators although depletion of each of them decreased pS2 mRNA expression in estradiol-treated MCF-7 cells. Moreover, progesterone receptor and cyclin D1 gene expression were decreased in SRC-3 small interfering RNA-treated cells. Expression of mRNA and protein levels for the antiapoptotic gene, Bcl-2 was dependent on SRC-3 expression, whereas Bcl-2 protein but not mRNA expression also was sensitive to SRC-1 depletion. Together these data indicate that the closely related p160 coactivators are not functionally redundant in breast cancer cells because they play gene-specific roles in regulating mRNA and protein expression, and they therefore are likely to make unique contributions to breast tumorigenesis.

scholarly journals Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells

Autophagy ◽  
2008 ◽  
Vol 4 (5) ◽  
pp. 669-679 ◽  
Author(s):  
Ugur Akar ◽  
Arturo Chaves-Reyez ◽  
Magaly Barria ◽  
Ana Tari ◽  
Angela Sanguino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Small Interfering Rna ◽  
Breast Cancer Cells ◽  
Autophagic Cell Death ◽  
Interfering Rna ◽  
Mcf 7

scholarly journals Biochanin A Promotes Proliferation that Involves a Feedback Loop of MicroRNA-375 and Estrogen Receptor Alpha in Breast Cancer Cells

2015 ◽  
Vol 35 (2) ◽  
pp. 639-646 ◽  
Author(s):  
Jian Chen ◽  
Bo Ge ◽  
Yong Wang ◽  
Yu Ye ◽  
Sien Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Feedback Loop ◽  
Biochanin A ◽  
Mrna Levels ◽  
Mcf 7

Background: Biochanin A and formononetin are O-methylated isoflavones that are isolated from the root of Astragalus membranaceus, and have antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. We performed in vivo and in vitro studies to further investigate the potential effect of biochanin A in promoting cell proliferation in estrogen receptor (ER)-positive cells, and to elucidate underlying mechanisms. Methods: ERα-positive breast cancer cells (T47D, MCF-7) were treated with biochanin A. The MTT assay and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ERα, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. Compared with the control, low biochanin A concentrations (2-6 μM) stimulated ERα-positive cell proliferation (T47D, MCF-7). The more sensitive T47D cells were used to study the relevant signaling pathway. Results: After treatment with biochanin A, ERα, miR-375, and Bcl-2 expression was significantly upregulated. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with biochanin A increased significantly. Conclusion: This study demonstrated that biochanin A promoted ERα-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ERα feedback loop.

scholarly journals Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu-Chen S. H. Yang ◽  
Zi-Lin Li ◽  
Tung-Yung Huang ◽  
Kuan-Wei Su ◽  
Chi-Yu Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Gene Expressions ◽  
Er Positive ◽  
Mcf 7

Estrogen (E2) has multiple functions in breast cancers including stimulating cancer growth and interfering with chemotherapeutic efficacy. Heteronemin, a marine sesterterpenoid-type natural product, has cytotoxicity on cancer cells. Breast cancer cell lines, MCF-7 and MDA-MB-231, were used for investigating mechanisms involved in inhibitory effect of E2 on heteronemin-induced anti-proliferation in breast cancer cells with different estrogen receptor (ER) status. Cytotoxicity was detected by cell proliferation assay and flow cytometry, gene expressions were determined by qPCR, mechanisms were investigated by Western blot and Mitochondrial ROS assay. Heteronemin exhibited potent cytotoxic effects against both ER-positive and ER-negative breast cancer cells. E2 stimulated cell growth in ER-positive breast cancer cells. Heteronemin induced anti-proliferation via suppressing activation of ERK1/2 and STAT3. Heteronemin suppressed E2-induced proliferation in both breast cancer cells although some gene expressions and anti-proliferative effects were inhibited in the presence of E2 in MCF-7 and MDA-MB-231 cells with a higher concentration of heteronemin. Heteromenin decreased the Bcl-2/Bax ratio to inhibit proliferation in MDA-MB-231 but not in MCF-7 cells. Both heteronemin and E2 increased mitochondrial reactive oxygen species but combined treatment reversed superoxide dismutase (SOD)s accumulation in MCF-7 cells. Heteronemin caused G0/G1 phase arrest and reduced the percentage of cells in the S phase to suppress cancer cell growth. In conclusion, Heteronemin suppressed both ER-positive and ER-negative breast cancer cell proliferation. Interactions between E2 and heteronemin in signal transduction, gene expressions, and biological activities provide insights into the complex pathways by which anti-proliferation is induced by heteronemin in E2-replete environments.

scholarly journals Gold Nanoparticles Increase PLK1-Specific Small Interfering RNA Transfection and Induce Apoptosis of Drug Resistance Breast Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Tian ◽  
Yunlei Zhang ◽  
Jing Pan ◽  
Nan Lu ◽  
Shouju Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Small Interfering Rna ◽  
Breast Cancer Cells ◽  
Low Cytotoxicity ◽  
Interfering Rna ◽  
Lipofectamine 2000 ◽  
Mcf 7

Drug resistance is a major barrier that limits the effectiveness of chemotherapies against breast cancer. Here, gold nanoparticles (GNPs) characterized by good dispersivity, high stability, low cytotoxicity, and simple synthesis were developed to deliver small interfering RNA (siRNA) against PLK1 (PLK1-siRNA) and overcome the drug resistance of breast cancer cells. Compared with the commonly used Lipofectamine 2000, GNPs showed higher PLK1-siRNA delivery efficiency and resulted in the remarkable gene silencing ofPLK1in drug resistance breast cancer cells MCF-7/MDR1 with low cytotoxicityin vitro. Moreover, delivery of PLK1-siRNA by GNPs could cause 14.23% apoptosis of MCF-7/MDR1 cells, which was apparently higher than 11.01% apoptosis conducted by Lipofectamine 2000. In addition, GNPs showed strong X-ray attenuation coefficient, indicating the potential theranostic application of this system. Therefore, this study disclosed an important step in the use of GNPs as transfection vector of siRNA that will be of great benefit to gene therapy against drug resistant cancer.

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