Estrogen regulation of anti-apoptotic Bcl-2 family member Mcl-1 expression in breast cancer cells.
Estrogen is implicated as an important factor in stimulating breast cancer cell proliferation, and presence of estrogen receptor (ER) is an indication of a good prognosis in breast cancer patients. Mcl-1 is an anti-apoptotic Bcl-2 family member that is often over expressed in breast tumors, correlat...
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doaj-f4107037b327497d8d2ade9fc5f69d722020-11-24T22:02:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e10036410.1371/journal.pone.0100364Estrogen regulation of anti-apoptotic Bcl-2 family member Mcl-1 expression in breast cancer cells.Jennifer L SchacterElizabeth S HensonSpencer B GibsonEstrogen is implicated as an important factor in stimulating breast cancer cell proliferation, and presence of estrogen receptor (ER) is an indication of a good prognosis in breast cancer patients. Mcl-1 is an anti-apoptotic Bcl-2 family member that is often over expressed in breast tumors, correlating with poor survival. In breast cancer, it was been previously shown that epidermal growth factor receptors up-regulate Mcl-1 but the role of estrogen in increasing Mcl-1 expression was unknown. In ERα positive cell lines MCF-7 and ZR-75, estrogen treatment increased Mcl-1 expression at both the protein and mRNA level. In two ERα negative cell lines, SK-BR-3 and MDA-MB-231, estrogen failed to increase in Mcl-1 protein expression. We found that ERα antagonists decreased estrogen mediated Mcl-1 expression at both the protein and mRNA level. Upon knockdown of ERα, Mcl-1 mRNA expression after estrogen treatment was also decreased. We also found that ERα binds to the Mcl-1 promoter at a region upstream of the translation start site containing a half ERE site. Streptavidin-pull down assay showed that both ERα and transcription factor Sp1 bind to this region. These results suggest that estrogen is involved in regulating Mcl-1 expression specifically through a mechanism involving ERα.http://europepmc.org/articles/PMC4074091?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jennifer L Schacter Elizabeth S Henson Spencer B Gibson |
spellingShingle |
Jennifer L Schacter Elizabeth S Henson Spencer B Gibson Estrogen regulation of anti-apoptotic Bcl-2 family member Mcl-1 expression in breast cancer cells. PLoS ONE |
author_facet |
Jennifer L Schacter Elizabeth S Henson Spencer B Gibson |
author_sort |
Jennifer L Schacter |
title |
Estrogen regulation of anti-apoptotic Bcl-2 family member Mcl-1 expression in breast cancer cells. |
title_short |
Estrogen regulation of anti-apoptotic Bcl-2 family member Mcl-1 expression in breast cancer cells. |
title_full |
Estrogen regulation of anti-apoptotic Bcl-2 family member Mcl-1 expression in breast cancer cells. |
title_fullStr |
Estrogen regulation of anti-apoptotic Bcl-2 family member Mcl-1 expression in breast cancer cells. |
title_full_unstemmed |
Estrogen regulation of anti-apoptotic Bcl-2 family member Mcl-1 expression in breast cancer cells. |
title_sort |
estrogen regulation of anti-apoptotic bcl-2 family member mcl-1 expression in breast cancer cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Estrogen is implicated as an important factor in stimulating breast cancer cell proliferation, and presence of estrogen receptor (ER) is an indication of a good prognosis in breast cancer patients. Mcl-1 is an anti-apoptotic Bcl-2 family member that is often over expressed in breast tumors, correlating with poor survival. In breast cancer, it was been previously shown that epidermal growth factor receptors up-regulate Mcl-1 but the role of estrogen in increasing Mcl-1 expression was unknown. In ERα positive cell lines MCF-7 and ZR-75, estrogen treatment increased Mcl-1 expression at both the protein and mRNA level. In two ERα negative cell lines, SK-BR-3 and MDA-MB-231, estrogen failed to increase in Mcl-1 protein expression. We found that ERα antagonists decreased estrogen mediated Mcl-1 expression at both the protein and mRNA level. Upon knockdown of ERα, Mcl-1 mRNA expression after estrogen treatment was also decreased. We also found that ERα binds to the Mcl-1 promoter at a region upstream of the translation start site containing a half ERE site. Streptavidin-pull down assay showed that both ERα and transcription factor Sp1 bind to this region. These results suggest that estrogen is involved in regulating Mcl-1 expression specifically through a mechanism involving ERα. |
url |
http://europepmc.org/articles/PMC4074091?pdf=render |
work_keys_str_mv |
AT jenniferlschacter estrogenregulationofantiapoptoticbcl2familymembermcl1expressioninbreastcancercells AT elizabethshenson estrogenregulationofantiapoptoticbcl2familymembermcl1expressioninbreastcancercells AT spencerbgibson estrogenregulationofantiapoptoticbcl2familymembermcl1expressioninbreastcancercells |
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