Progesterone agonists and antagonists induce down– and up–regulation of estrogen receptors and estrogen inducible genes in human breast cancer cell lines

1995 ◽  
Vol 10 (1) ◽  
pp. 47-54 ◽  
Author(s):  
G. Savoldi ◽  
F. Ferrari ◽  
G. Ruggeri ◽  
L. Sobek ◽  
A. Albertini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
T47d Cells ◽  
Hormone Sensitive ◽  
Mcf 7

The effects of the synthetic progestin R5020 and the antiprogestin RU486 on the cellular content of estrogen receptors (ER) and on cell responsiveness to estrogens, have been investigated in the sex hormone-sensitive human breast cancer cell lines MCF-7 and T47D. When T47D cells were treated with R5020 (Promegestone) (10–8 M), ER was down-regulated to about 50% of the control level in a time-dependent manner. Maximum down-regulation was observed after 24 hours and remained at this level for the next 24 hours. Dihydrotestosterone (DHT) or dexamethasone (DEX) had no effect on ER sites. R5020 also down-regulated, although to a lesser extent, ER in the MCF-7 cells which contain fewer progesterone receptor (PR) sites. When MCF-7 cells were transfected with a progesterone receptor expression vector (tMCF-7) to increase the number of PR sites, R5020 down-regulated the ER to a level similar to that reached in T47D cells. In both cell lines ER down-regulation was completely inhibited by a 10-fold molar excess of the antiprogestin RU486 (Mifepristone) (10–7 M). Surprisingly, when incubated with RU486 alone, T47D cells responded by up-regulating ER 2-4 fold. The functional relevance of inhibition and up-regulation of ER for the estrogen responsiveness of hormone-sensitive human breast cancer cells was tested by assaying the synthesis of an estrogen-regulated product, the PS2 protein. Estrogen induction of this protein was inhibited by at least 70% in T47D cells exposed to R5020 for 24 hours before estrogen administration and by about 25% in MCF-7 cells under the same conditions. A 55% inhibition was observed in tMCF-7 cells. Up-regulation of ER by RU486 in T47D cells led to an increase in the estrogen induction of PS2 by about 18-20% compared to RU486 untreated cells. These results indicate that the progestin and antiprogestin regulation of ER is functionally important for the estrogen responsiveness of breast cancer cells.

scholarly journals The role of miRNAs 34a, 146a, 320a and 542 in the synergistic anticancer effects of methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) with doxorubicin in breast cancer cells

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5577 ◽  
Author(s):  
Mohadeseh Hasanpourghadi ◽  
Nazia Abdul Majid ◽  
Mohd Rais Mustafa
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Mcf 7

Combination Index (CI) analysis suggested that MBIC and doxorubicin synergistically inhibited up to 97% of cell proliferation in ER+/PR+MCF-7 and triple negative MDA-MB-231 breast cancer cell lines. Moreover, treatment of the breast cancer cells with the combined drugs resulted in lower IC50 values in contrast to the individual drug treatment. Small noncoding microRNAs (miRNA) may function as non-mutational gene regulators at post-transcriptional level of protein synthesis. In the present study, the effect of the combined treatment of MBIC and doxorubicin on the expression level of several miRNAs including miR-34a, miR-146a, miR-320a and miR-542 were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. These miRNAs have the potential to alter the protein level of survivin, the anti-apoptotic protein and reduce the metastatic activity in human breast cancer cell lines by interfering with the nuclear accumulation of NF-κB. Our results demonstrated the several fold changes in expression of miRNAs, which is drug and cell line dependent. This finding demonstrated a functional synergistic network between miR-34a, miR-320a and miR-542 that are negatively involved in post-transcriptional regulation of survivin in MCF-7 cells. While in MDA-MB-231 cells, changes in expression level of miR-146a was correlated with inhibition of the nuclear translocation of NF-κB. The overall result suggested that alteration in protein level and location of survivin and NF-κB by miR-34a, miR-320a, miR-146a and miR-542, remarkably influenced the synergistic enhancement of combined MBIC and doxorubicin in treatment of aggressive and less aggressive human breast cancer cell lines.

scholarly journals Molecular and chemical characterization by Fourier transform infrared spectroscopy of human breast cancer cells with estrogen receptor expressed and not expressed

2010 ◽  
Vol 24 (5) ◽  
pp. 501-510 ◽  
Author(s):  
Leila Büttner Mostaço-Guidolin ◽  
Luciana Sayuri Murakami ◽  
Marina Ribeiro Batistuti ◽  
Auro Nomizo ◽  
Luciano Bachmann
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Chemical Characterization ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Mcf 7

The present study was designed to identify and compare the infrared absorption spectra of two human breast cancer cell lines: MCF-7 (estrogen receptor expressed, ER+) and SKBr3 (estrogen receptor non-expressed, ER–). Comparison between SKBr3 and MCF-7 cells revealed differences in the following absorption band areas: 1087 cm–1(DNA), 1397 cm–1(CH3), 1543 cm–1(amide II), 1651 cm–1(amide I), 2924 cm–1(fatty acids). Additionally, peak shifts were observed at 1122 cm–1(RNA), 1397 cm–1(CH3), 1651 cm–1(amide I), 2851 cm–1(fatty acids) and 2962 cm–1(fatty acids). An analysis of the ratio between band areas was conducted, in order to obtain an index that could effectively distinguish between these two cell lines. The following ratios were found: 1650 cm–1/1540 cm–1, 1650 cm–1/1740 cm–1, 1650 cm–1/1084 cm–1and 1120 cm–1/1084 cm–1. This work demonstrates that it is possible to distinguish between MCF-7 and SKBr3 cells through differences in their FTIR spectra. This work enables distinction between two cell lines from the same breast cancer.

scholarly journals New Isoflavanes from Spatholobus suberectus and Their Cytotoxicity against Human Breast Cancer Cell Lines

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3218 ◽  
Author(s):  
Fu Peng ◽  
Huan Zhu ◽  
Chun-Wang Meng ◽  
Yan-Rui Ren ◽  
Ou Dai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Spatholobus Suberectus ◽  
Mcf 7

The rattans of Spatholobus suberectus Dunn are a traditional Chinese medicine activating blood circulation and removing stasis. They have often been used for the traditional Chinese medicinal treatment of breast cancer in modern China. In this study, four novel isoflavanes (1–3 and 5) and four known analogues (4 and 6–8) were isolated from an ethanolic extract of the rattans of S. suberectus. Their structures were elucidated by extensive spectroscopic analyses and electronic circular dichroism studies. MCF-7 and MDA-MB-231 human breast cancer cell lines were used to evaluate the cytotoxic effects of the isolates. Interestingly, compounds 1 and 2 only inhibited the proliferation of MCF-7 cells, while compound 6 showed a selective cytotoxicity against MDA-MB-231 cells. However, compound 4 had significant cytotoxicity against both MCF-7 and MDA-MB-231 cell lines.

Peroxisome proliferator-activated receptor ? in the human breast cancer cell lines MCF-7 and MDA-MB-231

2002 ◽  
Vol 34 (4) ◽  
pp. 165-171 ◽  
Author(s):  
Kate M. Suchanek ◽  
Fiona J. May ◽  
Jodie A. Robinson ◽  
Won Jae Lee ◽  
Nicola A. Holman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Peroxisome Proliferator ◽  
Human Breast ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mcf 7

scholarly journals Calcitonin binding and degradation by two cultured human breast cancer cell lines (MCF 7 and T 47D)

1981 ◽  
Vol 196 (2) ◽  
pp. 513-520 ◽  
Author(s):  
D M Findlay ◽  
V P Michelangeli ◽  
J M Moseley ◽  
T J Martin
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Salmon Calcitonin ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Mcf 7

Two human breast cancer cell lines (MCF 7 and T 47D) possess calcitonin-responsive adenylate cyclase systems. Suspended cells of both lines specifically bound 125I-labelled salmon calcitonin with mean dissociation constants of 1.7 nM (MCF 7) and 1.4 nM (T 47D); mean receptor numbers were 5300 and 24400 per cell respectively. Measurement of specific binding to MCF 7 cells was obscured by rapid and substantial degradation of the labelled hormone. Degradation of 125I-labelled salmon calcitonin: (i) was of high capacity; (ii) lacked the specificity displayed by 125I-labelled salmon calcitonin binding to the same cells; and (iii) was not related to binding since cell incubation supernatants retained full degrading activity. The degrading activity was inhibited by corticotropin (1-24)-tetracosapeptide, insulin and bacitracin. Inclusion of bacitracin in the incubation resulted in apparently fewer numbers of lower affinity receptors on MCF 7 cells, whereas these parameters were identical to T 47D cells incubated in the presence or absence of bacitracin. Eel [2-aminosuberic acid 1,7]-calcitonin was resistant to proteolysis in the presence of either cell line. Analysis of hormone-receptor interactions with calcitonin-responsive cells should take account of potent calcitonin-degrading activities in some cell lines.

scholarly journals Cellular and molecular crosstalk between leptin receptor and estrogen receptor-α in breast cancer: molecular basis for a novel therapeutic setting

2010 ◽  
Vol 17 (2) ◽  
pp. 373-382 ◽  
Author(s):  
Roberta Fusco ◽  
Mario Galgani ◽  
Claudio Procaccini ◽  
Renato Franco ◽  
Giuseppe Pirozzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Leptin Receptor ◽  
Estrogen Receptor Α ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Increased Risk ◽  
Mcf 7

Obesity is associated with an increased risk of breast cancer. A number of adipocytokines are increased in obesity causing low-level chronic inflammation associated with an increased risk of tumors. The adipocytokine leptin shows profound anti-obesity and pro-inflammatory activities. We have hypothesized that in common obesity, high circulating leptin levels might contribute to an increased risk of breast cancer by affecting mammary cell proliferation and survival. Leptin exerts its activity not only through leptin receptor (LepR), but also through crosstalk with other signaling systems implicated in tumorigenesis. In this study, we focused our attention on the relationship between the leptin/LepR axis and the estrogen receptor-α (ERα). To this aim, we utilized two human breast cancer cell lines, one ERα-positive cell line (MCF 7) and the other ERα-negative cell line (MDA-MB 231). We observed that the two cell lines had a different sensitivity to recombinant leptin (rleptin): on MCF 7 cells, rleptin induced a strong phosphorylation of the signal transducer and activator of transcription (STAT) 3 and of the extracellular related kinase 1/2 pathways with an increased cell viability and proliferation associated with an increased expression of ERα receptor. This response was not present in the MDA-MB 231 cells. The effects induced by leptin were lost when LepR was neutralized using either a monoclonal inhibitory antibody to LepR or LepR gene-silencing siRNA. These data suggest that there is a bidirectional communication between LepR and ERα, and that neutralization and/or inactivation of LepR inhibits proliferation and viability of human breast cancer cell lines. This evidence was confirmed by ex vivo studies, in which we analyzed 33 patients with breast cancer at different stages of disease, and observed that there was a statistically significant correlation between the expression of LepR and ERα. In conclusion, this study suggests a crosstalk between LepR and ERα, and could envisage novel therapeutic settings aimed at targeting the LepR in breast cancers.

scholarly journals The Effect of Rapamycin on Oxidative Stress in MCF-7 and MDA MB-231 Human Breast Cancer Cell Lines

2016 ◽  
Vol 11 (3) ◽  
Author(s):  
Hadi Kalantar ◽  
Masoumeh Sabetkasaei ◽  
Ali Shahriari ◽  
Mostafa Haj Molla Hoseini ◽  
Siavash Mansouri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Mcf 7
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