title: Estrogen regulation of anti-apoptotic Bcl-2 family member Mcl-1 expression in breast cancer cells.
abstract: 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.
authors: Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada; Manitoba Institute of Cell Biology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors: Jennifer L
authors: JL
authors: Schacter
authors: Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada; Manitoba Institute of Cell Biology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors: Elizabeth S
authors: ES
authors: Henson
authors: Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada; Manitoba Institute of Cell Biology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors: Spencer B
authors: SB
authors: Gibson
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D023061:Gene Order; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor