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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4074091?pdf=render |
| _version_ | 1819239134547410944 |
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| author | Jennifer L Schacter Elizabeth S Henson Spencer B Gibson |
| author_facet | Jennifer L Schacter Elizabeth S Henson Spencer B Gibson |
| author_sort | Jennifer L Schacter |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T13:47:18Z |
| format | Article |
| id | doaj.art-f4107037b327497d8d2ade9fc5f69d72 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T13:47:18Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f4107037b327497d8d2ade9fc5f69d722022-12-21T17:44:41ZengPublic 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 |
| 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 |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC4074091?pdf=render |
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