scholarly journals Histone Deacetylase Inhibitors Stimulate Dedifferentiation of Human Breast Cancer Cells Through WNT/β-Catenin Signaling

Stem Cells ◽  
2012 ◽  
Vol 30 (11) ◽  
pp. 2366-2377 ◽  
Author(s):  
Bisrat G. Debeb ◽  
Lara Lacerda ◽  
Wei Xu ◽  
Richard Larson ◽  
Travis Solley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Histone Deacetylase Inhibitors ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals Oestrogen receptor alpha increases p21(WAF1/CIP1) gene expression and the antiproliferative activity of histone deacetylase inhibitors in human breast cancer cells

2003 ◽  
Vol 179 (1) ◽  
pp. 41-53 ◽  
Author(s):  
R Margueron ◽  
A Licznar ◽  
G Lazennec ◽  
F Vignon ◽  
V Cavailles
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
P21 Waf1

We analysed the antiproliferative activity of various histone deacetylase (HDAC) inhibitors such as trichostatin A (TSA) on human breast cancer cells. We observed a lower sensitivity to HDAC inhibition for oestrogen receptor negative (ER-) versus positive (ER+) cell lines. This differential response was associated neither with a modification of drug efflux via the multidrug resistance system nor with a global modification of histone acetyltransferase (HAT)/HDAC activities. In contrast, we demonstrated that in ER+ breast cancer cells the p21(WAF1/CIP1) gene was more sensitive to TSA regulation and was expressed at higher levels. These differences were observed both in transient transfection experiments and on the endogenous p21(WAF1/CIP1) gene. The Sp1 transcription factor, which was shown to interact in vitro with both class I and class II HDACs, is sufficient to confer the differential sensitivity to TSA and participated in the control of p21(WAF1/CIP1) basal expression. Finally, re-expression of ERalpha following adenoviral infection of ER- breast cancer cells increased both p21(WAF1/CIP1) protein accumulation and the growth inhibitory activity of TSA. Altogether, our results highlight the key role of ERalpha and p21(WAF1/CIP1) gene expression in the sensitivity of breast cancer cells to hyperacetylating agents.

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