Document Detail


Loss of ERα and FOXA1 expression in a progression model of luminal type breast cancer: insights from PyMT transgenic mouse model.
MedLine Citation:
PMID:  20878115     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The classification of breast cancer into multiple molecular subtypes has necessitated the need for biomarkers that can assess tumor progression and the effects of chemopreventive agents on specific breast cancer subtypes. The goal of this study was to identify biomarkers whose expression are altered along with estrogen receptor α (ERα) in the polyoma middle-T antigen (PyMT) transgenic model of breast cancer and to investigate the chemopreventive activity of phenethyl isothiocyanate (PEITC). The diet of PyMT female mice was fortified with PEITC (8 mmol/kg) and the mammary streak and/or gross tumors and metastases in lungs were subjected to immunohistochemical analyses for ERα, FOXA1, and GATA-3. FOXA1 is associated with luminal type A cancers, while GATA-3 is a marker of luminal progenitor cell differentiation. In both control and PEITC-treated groups, there was a progressive loss of ERα and FOXA1 but persistence of GATA-3 expression indicating that the tumors retain luminal phenotype. Overall, the PyMT induced tumors exhibited the entire gamut of phenotypes from ERα+/FOXA1+/GATA-3+ tumors in the early stage to ERα±/FOXA1-/GATA-3+ in the late stage. Thus, PyMT model serves as an excellent model for studying progression of luminal subtype tumors. PEITC treated animals had multiple small tumors, indicating delay in tumor progression. Although these tumors were histologically similar to those in controls, there was a lower expression of these biomarkers in normal luminal cells indicating delay in tumor initiation. In in vitro studies, PEITC depleted AldeFluor-positive putative stem/progenitor cells, which may partly be responsible for the delay in tumor initiation.
Authors:
Kasi McCune; Rutika Mehta; Mangesh A Thorat; Sunil Badve; Harikrishna Nakshatri
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Oncology reports     Volume:  24     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-29     Completed Date:  2011-02-18     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1233-9     Citation Subset:  IM    
Affiliation:
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticarcinogenic Agents / pharmacology
Cell Growth Processes / drug effects
Cell Line, Tumor
Disease Models, Animal
Disease Progression
Estrogen Receptor alpha / biosynthesis,  deficiency*,  genetics
Female
GATA3 Transcription Factor / biosynthesis,  genetics
Gene Expression Regulation, Neoplastic
Hepatocyte Nuclear Factor 3-alpha / biosynthesis,  deficiency*,  genetics
Isothiocyanates / pharmacology
Mammary Neoplasms, Experimental / genetics,  metabolism*,  pathology*,  prevention & control
Mice
Mice, Transgenic
Neoplastic Stem Cells / drug effects
Prognosis
Grant Support
ID/Acronym/Agency:
CA111198/CA/NCI NIH HHS; R03 CA123561/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Estrogen Receptor alpha; 0/Foxa1 protein, mouse; 0/GATA3 Transcription Factor; 0/Hepatocyte Nuclear Factor 3-alpha; 0/Isothiocyanates; 6U7TFK75KV/phenethyl isothiocyanate
Comments/Corrections

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