Transcription factor Ets1 cooperates with estrogen receptor α to stimulate estradiol-dependent growth in breast cancer cells and tumors

Autor: Sara R. Anglin, Liza E. O’Donoghue, Charles H. C. Halsey, Brian T. Kalet, Laura S. Chubb, Dawn L. Duval, Anne V. Handschy, Christopher Korch
Rok vydání: 2012
Předmět:
Mouse
lcsh:Medicine
Estrogen receptor
Gene Expression
Biochemistry
Mice
0302 clinical medicine
Molecular cell biology
Cell Movement
Basic Cancer Research
Pathology
lcsh:Science
Tumor Stem Cell Assay
0303 health sciences
Multidisciplinary
Estradiol
Animal Models
Tumor Burden
Platelet Endothelial Cell Adhesion Molecule-1
Oncology
030220 oncology & carcinogenesis
MCF-7 Cells
Medicine
Female
Protein Binding
Research Article
DNA transcription
Breast Neoplasms
Biology
Response Elements
Cell Growth
Proto-Oncogene Protein c-ets-1
03 medical and health sciences
Model Organisms
Diagnostic Medicine
Cell Line
Tumor
Coactivator
Progesterone receptor
Animals
Humans
Protein Interactions
Transcription factor
Estrogen receptor beta
030304 developmental biology
Cell Proliferation
Hormone response element
lcsh:R
Estrogen Receptor alpha
Proteins
Molecular biology
Ki-67 Antigen
Nuclear receptor
Multiprotein Complexes
lcsh:Q
Estrogen receptor alpha
Biomarkers
General Pathology
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 7, p e68815 (2013)
ISSN: 1932-6203
Popis: The purpose of this study was to explore the role of transcription factor Ets1 in estrogen receptor α (ERα)-positive breast cancer progression. We expressed human Ets1 or empty vector in four human ERα-positive breast cancer cell lines and observed increased colony formation. Further examination of cellular responses in stable Ets1-expressing MCF7 clones displayed increased proliferation, migration, and invasion. Ets1-expressing MCF7 tumors grown in the mammary fat pads of nude mice exhibited increased rates of tumor growth (7.36±2.47 mm(3)/day) compared to control MCF7 tumors (2.52±1.70 mm(3)/day), but maintained their dependence on estradiol for tumor growth. Proliferation marker Ki-67 staining was not different between control and Ets1-expressing tumors, but Ets1-expressing tumors exhibited large necrotic centers and elevated apoptotic staining. Ets1 was shown to cooperate with ERα and the p160 nuclear receptor coactivator (NCOA/SRC) family to increase activation of a consensus estrogen response element luciferase reporter construct. Ets1-expressing MCF7 cells also exhibited elevated expression of the ERα target genes, progesterone receptor and trefoil factor 1. Using GST-pulldown assays, Ets1 formed stable complexes containing both ERα and p160 nuclear receptor coactivators. Taken together, these data suggest that the Ets1-dependent estradiol sensitization of breast cancer cells and tumors may be partially due to the ability of Ets1 to cooperate with ERα and nuclear receptor coactivators to stimulate transcriptional activity of estrogen-dependent genes.
Databáze: OpenAIRE
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