scholarly journals Antiestrogen-resistant human breast cancer cells require activated Protein Kinase B/Akt for growth

2005 ◽  
Vol 12 (3) ◽  
pp. 599-614 ◽  
Author(s):  
T Frogne ◽  
J S Jepsen ◽  
S S Larsen ◽  
C K Fog ◽  
B L Brockdorff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Neutralizing Antibodies ◽  
Breast Cancer Cells ◽  
Resistant Cell ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Mcf 7

Development of acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. The IGF system plays a profound role in many cancer types, including breast cancer. Thus, overexpression and/or constitutive activation of the IGF-I receptor (IGF-IR) or different components of the IGF-IR signaling pathway have been reported to render breast cancer cells less estrogen dependent and capable of sustaining cell proliferation in the presence of antiestrogens. In this study, growth of the antiestrogen-sensitive human breast cancer cell line MCF-7 was inhibited by treatment with IGF-IR-neutralizing antibodies. In contrast, IGF-IR-neutralizing antibodies had no effect on growth of two different antiestrogen-resistant MCF-7 sublines. A panel of antiestrogen-resistant cell lines was investigated for expression of IGF-IR and either undetectable or severely reduced IGF-IR levels were observed. No increase in insulin receptor substrate 1 (IRS-1) or total PKB/Akt (Akt) was detected in the resistant cell lines. However, a significant increase in phosphorylated Akt (pAkt) was found in four of six antiestrogen-resistant cell lines. Overexpression of pAkt was associated with increased Akt kinase activity in both a tamoxifen- and an ICI 182,780-resistant cell line. Inhibition of Akt phosphorylation by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin or the Akt inhibitor SH-6 (structurally modified phosphatidyl inositol ether liquid analog PIA 6) resulted in a more pronounced growth inhibitory effect on the antiestrogen-resistant cells compared with the parental cells, suggesting that signaling via Akt is required for antiestrogen-resistant cell growth in at least a subset of our antiestrogen-resistant cell lines. PTEN expression and activity was not decreased in cell lines overexpressing pAkt. Our data demonstrate that Akt is a target for treatment of antiestrogen-resistant breast cancer cell lines and we suggest that antiestrogen-resistant breast cancer patients may benefit from treatment targeted to inhibit Akt signaling.

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.

Synergistic inhibition of breast cancer cell lines with the combination of a dual inhibitor of EGFR/HER-2/neu and a Bcl-2 inhibitor

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13100-13100
Author(s):  
L. Witters ◽  
A. Witkoski ◽  
M. Planas-Silva ◽  
J. Viallet ◽  
M. S. Berger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Dual Inhibitor ◽  
Her 2 ◽  
Mcf 7

13100 Background: The epidermal growth factor receptor (EGFR; ErbB1) and HER-2/neu (ErbB2), members of the ErbB family of receptor tyrosine kinases, are overexpressed in a variety of human tumors and overexpression generally correlates with poor prognosis and decreased survival. Use of inhibitors of these receptors as monotherapies, e.g., trastuzumab, Iressa, and erlotinib, has led to advances in treatment, but many patients do not respond or develop resistance. The anti-apoptotic protein, Bcl-2, is also overexpressed in a number of human tumors. Inhibitors of Bcl-2 induce apoptosis and sensitize cancer cells to other therapies. This study assesses the effects of a combination of a reversible inhibitor of both EGFR and HER-2/neu that is similar to lapatinib (GW2974) and a pan inhibitor of the Bcl-2 family (GX15–070: Gemin X Biotechnologies, Inc.) on the growth of human breast cancer cells. Methods: The MCF-7 human breast cancer cell line transfected with a control vector, MCF/neo, and the HER-2/neu transfected MCF-7 cell line, MCF/18, were treated with various concentrations of GW2974 (0.25–10 μM) and/or the GX15–070 pan Bcl-2 inhibitor (50–500 nM). After a 3 day exposure, cell number was determined using the colorimetric MTT tetrazolium dye assay. Percent of control was normalized to corresponding concentrations of the solvent for both agents (DMSO). Results: Treatment with the GW2974 dual inhibitor or the GX15–070 pan Bcl-2 inhibitor resulted in dose-dependent growth inhibition in both the control and HER-2/neu transfected MCF-7 cell lines. The combination of both agents produced synergistic growth inhibition in both cell lines as confirmed by isobologram analysis. Conclusions: This study has demonstrated synergy with the combination of a dual inhibitor of EGFR and HER-2/neu and an inhibitor of Bcl-2 in control and HER-2/neu overexpressing MCF-7 human breast cancer cells. This finding warrants an evaluation of this combination in clinical trials for the treatment of patients with metastatic breast cancer. [Table: see text]

The Hedgehog signalling pathway mediates drug response of MCF-7 mammosphere cells in breast cancer patients

2015 ◽  
Vol 129 (9) ◽  
pp. 809-822 ◽  
Author(s):  
Miao He ◽  
Yingzi Fu ◽  
Yuanyuan Yan ◽  
Qinghuan Xiao ◽  
Huizhe Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Human Breast Cancer ◽  
Drug Response ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Hedgehog Signalling ◽  
Hedgehog Signalling Pathway ◽  
Xenograft Mice ◽  
Mcf 7

Our study showed that Hh signalling activation contributed to BCSC-mediated chemoresistance in cultured breast cancer MCF-7 MS cells, in xenograft mice and in human breast cancer patients.

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 Increased Soluble CrkL in Serum of Breast Cancer Patients Is Associated with Advanced Disease

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 961 ◽  
Author(s):  
Srimeenakshi Srinivasan ◽  
Biana Godin
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Advanced Disease ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Human Breast

Over-expression of Crk-like protein (CrkL), an intracellular adaptor protein, in breast cancer biopsies has been linked to poor prognosis. CrkL can be secreted from cancer cells binding to β1 integrin on the cell membrane. In this study, we evaluated, for the first time, the levels of soluble CrkL in serum of breast cancer patients. Expression of CrkL and secreted fractions from human breast cancer cell lines and clinical patient samples were assessed by immunohistochemistry and Enzyme Linked Immuno-Sorbent Assay (ELISA). CrkL levels in tissues and sera of patients with different disease stages were compared and statistically analyzed by Chi-square test and Student’s t-test. Culture media from human breast cancer cell lines SUM159, MDA-MB231, and MCF7 showed over a 21-, 15-, and 11-fold higher concentration of soluble CrkL as compared to normal breast epithelium cell line MCF10A. Expression of CrkL was elevated in 85% of breast tumor tissue sections. Serum levels of CrkL were significantly higher in breast cancer patients than in healthy donors. All patients with metastatic disease had significantly elevated concentration of soluble CrkL in the serum with on average three-fold increase from the baseline. The data suggest that soluble fraction of CrkL can be further evaluated as a serum biomarker for advanced disease in breast cancer patients.

scholarly journals Antiproliferative activity of natural coumarins from Calophyllum incrasaptum M.R Henderson-Wyatt Smith against human breast cancer cells MCF

2018 ◽  
Vol 154 ◽  
pp. 04003
Author(s):  
Jamilah Abbas ◽  
Linar Z Udin ◽  
Muhammad Hanafi
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Alamar Blue ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

Objective: to evaluated the antiproliferative activity of natural coumarin from Calophyllum incrasaptum M.R Henderson-Wytt Smith against human breast cancer cells MCF-7. Methode : Coumarin from ethyl acetate fraction of C. incrasaptum M.R Henderson-Wyatt Smith was isolated by coloumn chromatographyic and structure elucidated by using spectroscopic methods and isolate compound was evaluated for their antiproliferative activities in the alamar blue assay. Result: Coumarin have antiproliferative activity against MCF-7 cancer cell lines through alamar blue assay for 4 h after treatment. Conclusions: coumarin showed good activity against cancer cell lines with IC50 value of 2.23 μg/mL.

scholarly journals Calycosin Inhibits the Migration and Invasion of Human Breast Cancer Cells by Down-Regulation of Foxp3 Expression

2017 ◽  
Vol 44 (5) ◽  
pp. 1775-1784 ◽  
Author(s):  
Shuangxi Li ◽  
Yafei Wang ◽  
Chan Feng ◽  
Guoli Wu ◽  
Yu Ye ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Higher Doses ◽  
Mcf 7

Background/Aims: Calycosin, a phytoestrogenic compound, has recently emerged as a promising antitumor drug. It has been shown that calycosin suppresses growth and induces apoptosis of breast cancer cells. However, the effect of calycosin on migration and invasion of breast cancer cells and the underlying molecular mechanisms have not been elucidated. Methods: Human breast cancer cells MCF-7 and T47D were treated with, or without, different doses (0, 6.25, 12.5, 25, 50, 100 or 150 μM) of calycosin, and the viability of different groups was determined by MTT assay. Next, the inhibitory effect of higher doses (50, 100 or 150 μM) of calycosin on migration and invasion of the two cell lines was determined by wound healing and transwell assay. The relative expression levels of forkhead box P3 (Foxp3), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in MCF-7 and T47D cells were determined by quantitative RT-PCR and Western blot. Results: Treatment with lower doses (6.25 or 12.5 μM) promoted proliferation of breast cancer cells, but with higher doses significantly reduced the viability of MCF-7 and T47D cells. Furthermore, higher doses of calycosin were found to inhibit migration and invasion of the two cell lines in a dose-dependent manner. Additionally, treatment with a higher dose of calycosin significantly reduced the expression levels of Foxp3, followed by down-regulation of VEGF and MMP-9 in both MCF-7 and T47D breast cancer cells. Conclusion: Treatment with a higher dose of calycosin tends to reduce migration and invasion capacity of human breast cancer cells, by targeting Foxp3-mediated VEGF and MMP-9 expression.

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