The ability of oestrogen to modulate the effects of cytotoxic drugs in human breast cancer cells: influence of oestrogen receptor status and choice of drug

1987 ◽  
Vol 15 (2) ◽  
pp. 242-243
Author(s):  
ROBERT CLARKE ◽  
HENDRIK W. VAN DEN BERG ◽  
RICHARD F. MURPHY
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Cytotoxic Drugs ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Oestrogen Receptor Status ◽  
Receptor Status

scholarly journals Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells

Open Biology ◽  
2016 ◽  
Vol 6 (12) ◽  
pp. 150262 ◽  
Author(s):  
Chin-Yo Lin ◽  
Erica L. Kleinbrink ◽  
Fabien Dachet ◽  
Juan Cai ◽  
Donghong Ju ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Signalling Pathways ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are transcripts of a recently discovered class of genes which do not code for proteins. LncRNA genes are approximately as numerous as protein-coding genes in the human genome. However, comparatively little remains known about lncRNA functions. We globally interrogated changes in the lncRNA transcriptome of oestrogen receptor positive human breast cancer cells following treatment with oestrogen, and identified 127 oestrogen-responsive lncRNAs. Consistent with the emerging evidence that most human lncRNA genes lack homologues outside of primates, our evolutionary analysis revealed primate-specific lncRNAs downstream of oestrogen signalling. We demonstrate, using multiple functional assays to probe gain- and loss-of-function phenotypes in two oestrogen receptor positive human breast cancer cell lines, that two primate-specific oestrogen-responsive lncRNAs identified in this study (the oestrogen-repressed lncRNA BC041455, which reduces cell viability, and the oestrogen-induced lncRNA CR593775, which increases cell viability) exert previously unrecognized functions in cell proliferation and growth factor signalling pathways. The results suggest that oestrogen-responsive lncRNAs are capable of altering the proliferation and viability of human breast cancer cells. No effects on cellular phenotypes were associated with control transfections. As heretofore unappreciated components of key signalling pathways in cancers, including the MAP kinase pathway, lncRNAs hence represent a novel mechanism of action for oestrogen effects on cellular proliferation and viability phenotypes. This finding warrants further investigation in basic and translational studies of breast and potentially other types of cancers, has broad relevance to lncRNAs in other nuclear hormone receptor pathways, and should facilitate exploiting and targeting these cell viability modulating lncRNAs in post-genomic therapeutics.

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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