Resistance of primary breast cancer cells with enhanced pluripotency and stem cell activity to sex hormonal stimulation and suppression

2018 ◽  
Vol 105 ◽  
pp. 84-93 ◽  
Author(s):  
Mostafa Nasr ◽  
Mohamed Farghaly ◽  
Tarek Elsaba ◽  
Mohamed El-Mokhtar ◽  
Radwa Radwan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Primary Breast Cancer ◽  
Breast Cancer Cells ◽  
Cell Activity ◽  
Hormonal Stimulation ◽  
Stem Cell Activity

The palladacycle, AJ-5, exhibits anti-tumour and anti-cancer stem cell activity in breast cancer cells

2015 ◽  
Vol 357 (1) ◽  
pp. 206-218 ◽  
Author(s):  
Saeb Aliwaini ◽  
Jade Peres ◽  
Wendy L. Kröger ◽  
Angelique Blanckenberg ◽  
Jo de la Mare ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Activity ◽  
Anti Cancer ◽  
Stem Cell Activity

Antitumor and anticancer stem cell activity of a poly ADP-ribose polymerase inhibitor olaparib in breast cancer cells

Breast Cancer ◽  
2012 ◽  
Vol 21 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Toshiro Shimo ◽  
Junichi Kurebayashi ◽  
Naoki Kanomata ◽  
Tetsumasa Yamashita ◽  
Yuji Kozuka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Activity ◽  
Stem Cell Activity ◽  
Polymerase Inhibitor

Anti-cancer stem cell activity of the CDK4/6 inhibitor palbociclib in breast cancer cells

The Breast ◽  
2019 ◽  
Vol 44 ◽  
pp. S28
Author(s):  
E. Kishino ◽  
R. Ogata ◽  
W. Saitoh ◽  
Y. Koike ◽  
Y. Ohta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Activity ◽  
Anti Cancer ◽  
Stem Cell Activity

Anti-cell growth and anti-cancer stem cell activity of the CDK4/6 inhibitor palbociclib in breast cancer cells

Breast Cancer ◽  
2019 ◽  
Vol 27 (3) ◽  
pp. 415-425 ◽  
Author(s):  
Emi Kishino ◽  
Ryohei Ogata ◽  
Wataru Saitoh ◽  
Yoshikazu Koike ◽  
Yusuke Ohta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cell Growth ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Activity ◽  
Anti Cancer ◽  
Stem Cell Activity

scholarly journals The Milk Protein Alpha-Casein Suppresses Triple Negative Breast Cancer Stem Cell Activity Via STAT and HIF-1alpha Signalling Pathways in Breast Cancer Cells and Fibroblasts

2019 ◽  
Vol 24 (3) ◽  
pp. 245-256 ◽  
Author(s):  
Kirsten E. L. Garner ◽  
Nathan J. Hull ◽  
Andrew H. Sims ◽  
Rebecca Lamb ◽  
Robert B. Clarke
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Cell Activity ◽  
Signalling Pathways ◽  
Activated Fibroblasts

Abstract Triple negative breast cancer (TNBC) is the most lethal breast cancer subtype. Extended periods of lactation protect against breast cancer development, but the mechanisms underlying this protection are unknown. We examined the effects of the milk protein alpha-casein over expression in the triple negative MDA-MB-231 breast cancer cell line. The effects of recombinant alpha-casein added exogenously to MDA-MB-231 breast cancer cells, and immortalised human fibroblasts were also investigated. We used transcriptional reporters to understand the signalling pathways downstream of alpha-casein in breast cancer cells and these fibroblasts that were activated by breast cancer cells. To extend our findings to the clinical setting, we analysed public gene expression datasets to further understand the relevance of these signalling pathways in triple negative breast cancer cells and patient samples. Finally, we used small molecular inhibitors to target relevant pathways and highlight these as potential candidates for the treatment of TN breast cancer. High levels of alpha-casein gene expression were predictive of good prognosis across 263 TNBC patient tumour samples. Alpha-casein over expression or exogenous addition reduces cancer stem cell (CSC) activity. HIF-1alpha was identified to be a key downstream target of alpha-casein, in both breast cancer cells and activated fibroblasts, and STAT transcription factors to be upstream of HIF-1alpha. Interestingly, HIF-1alpha is regulated by STAT3 in breast cancer cells, but STAT1 is the regulator of HIF-1alpha in activated fibroblasts. In analysis of 573 TNBC patient samples, alpha-casein expression, inversely correlated to HIF-1alpha, STAT3 and STAT1. STAT1 and STAT3 inhibitors target HIF-1alpha signalling in activated fibroblasts and MDA-MB-231 breast cancer cells respectively, and also abrogate CSC activities. Our findings provide an explanation for the protective effects of lactation in TNBC. Clinical data correlates high alpha-casein expression with increased recurrence-free survival in TNBC patients. Mechanistically, alpha-casein reduces breast cancer stem cell activity in vitro, and STAT3 and STAT1 were identified as regulators of pro-tumorigenic HIF-1alpha signalling in breast cancer cells and fibroblasts respectively.

scholarly journals The milk protein alpha-casein suppresses triple negative breast cancer stem cell activity via STAT and HIF-1alpha signalling pathways in breast cancer cells and fibroblasts

2019 ◽  
Author(s):  
Kirsten EL Garner ◽  
Rebecca Lamb ◽  
Andrew H Sims ◽  
Robert B Clarke
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Cell Activity ◽  
Signalling Pathways ◽  
Activated Fibroblasts

Triple negative breast cancer (TNBC) is the most lethal breast cancer subtype. Extended periods of lactation protect against breast cancer development, but the mechanisms underlying this protection are unknown. We examined the effects of the milk protein alpha-casein over expression in the triple negative MDA-MB-231 breast cancer cell line. The effects of recombinant alpha-casein added exogenously to MDA-MB-231 breast cancer cells, and immortalised human fibroblasts were also investigated. We used transcriptional reporters to understand the signalling pathways downstream of alpha-casein in breast cancer cells and these fibroblasts that were activated by breast cancer cells. To extend our findings to the clinical setting, we analysed public gene expression datasets to further understand the relevance of these signalling pathways in triple negative breast cancer cells and patient samples. Finally, we used small molecular inhibitors to target relevant pathways and highlight these as potential candidates for the treatment of TN breast cancer. High levels of alpha-casein gene expression were predictive of good prognosis across 263 TNBC patient tumour samples. Alpha-casein over expression or exogenous addition reduces cancer stem cell (CSC) activity. HIF-1alpha was identified to be a key downstream target of alpha-casein, in both breast cancer cells and activated fibroblasts, and STAT transcription factors to be upstream of HIF-1alpha. Interestingly, HIF-1alpha is regulated by STAT3 in breast cancer cells, but STAT1 is the regulator of HIF-1alpha in activated fibroblasts. In analysis of 573 TNBC patient samples, alpha-casein expression, inversely correlated to HIF-1alpha, STAT3 and STAT1. STAT1 and STAT3 inhibitors target HIF-1alpha signalling in activated fibroblasts and MDA-MB-231 breast cancer cells respectively, and also abrogate CSC activities. Our findings provide an explanation for the protective effects of lactation in TNBC. Clinical data correlates high alpha-casein expression with increased recurrence-free survival in TNBC patients. Mechanistically, alpha-casein reduces breast cancer stem cell activity in vitro, and STAT3 and STAT1 were identified as regulators of pro-tumorigenic HIF-1alpha signalling in breast cancer cells and fibroblasts respectively.

scholarly journals Anti-cancer stem cell activity of a hedgehog inhibitor GANT61 in estrogen receptor-positive breast cancer cells

2017 ◽  
Vol 108 (5) ◽  
pp. 918-930 ◽  
Author(s):  
Junichi Kurebayashi ◽  
Yoshikazu Koike ◽  
Yusuke Ohta ◽  
Wataru Saitoh ◽  
Tetsumasa Yamashita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Stem Cell ◽  
Breast Cancer Cells ◽  
Cell Activity ◽  
Anti Cancer ◽  
Stem Cell Activity ◽  
Estrogen Receptor Positive ◽  
Hedgehog Inhibitor ◽  
Positive Breast Cancer

Anti-cancer stem cell activity of the hedgehog inhibitor GANT61 in ER-positive breast cancer cells

The Breast ◽  
2017 ◽  
Vol 32 ◽  
pp. S39
Author(s):  
J. Kurebayashi ◽  
Y. Koike ◽  
Y. Ohta ◽  
W. Saitoh ◽  
T. Yamashita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Breast Cancer Cells ◽  
Cell Activity ◽  
Anti Cancer ◽  
Stem Cell Activity ◽  
Er Positive ◽  
Hedgehog Inhibitor ◽  
Positive Breast Cancer
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