Document Detail


Regulation of nuclear receptor and cofactor expression in breast cancer cell lines.
MedLine Citation:
PMID:  12656669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The aim of this study was to compare the expression profile of nuclear receptors (NRs) and cofactors in different breast cancer cell lines as well as their regulation by estradiol, insulin and progestin R5020. METHODS: Expression of NRs and cofactors were determined from MCF-7, T-47D and ZR-75-1 breast cancer cell lines. Multiprobe ribonuclease protection assay and real-time RT-PCR were used to quantitate mRNA levels of steroid receptors, vitamin D receptors (VDR) and retinoic acid receptors (RAR) and cofactors: amplified in breast cancer-1, cyclic AMP response element binding protein (CBP), p300/CBP-associated factor, p300, nuclear receptor corepressor and silencing mediator of repressed transcription. RESULTS: Basal expression levels of NRs and cofactors varied depending on the cell line. Cell line-specific regulation of androgen receptor, estrogen receptor-alpha (ERalpha), RARalpha, RARgamma and VDR expression was observed after estradiol treatment. Likewise, differences in the regulation of ERalpha, RARalpha and VDR expression after R5020 treatment were observed. We did not observe significant regulation of cofactor expression after estradiol, insulin or progestin treatment in any cell line analyzed. CONCLUSIONS: The results showed that not only is the expression profile of the NRs and cofactors cell line specific but also the regulation of NR expression. Thus the determinants of the ligand action (receptor and cofactor expression) varied considerably among different cell clones of the breast cancer cells. This suggested a gradient of NR-ligand sensitivities in the hormone-dependent breast cancers, which produces an additional challenge in developing novel ligands for hormone replacement therapy and breast cancer treatment.
Authors:
Annika Vienonen; Susanna Miettinen; Tommi Manninen; Lucia Altucci; Emmanuelle Wilhelm; Timo Ylikomi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of endocrinology / European Federation of Endocrine Societies     Volume:  148     ISSN:  0804-4643     ISO Abbreviation:  Eur. J. Endocrinol.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-03-26     Completed Date:  2003-05-15     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9423848     Medline TA:  Eur J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  469-79     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Medical School, University of Tampere, FIN-33014 Tampere, Finland. annika.vienonen@uta.fi
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MeSH Terms
Descriptor/Qualifier:
Acetyltransferases / genetics
Breast Neoplasms / metabolism*
Cell Cycle Proteins / genetics
Cyclic AMP Response Element-Binding Protein / genetics
Estradiol / pharmacology
Gene Expression Regulation, Neoplastic* / drug effects
Histone Acetyltransferases
Humans
Insulin / pharmacology
Nuclear Proteins / genetics
Nuclear Receptor Co-Repressor 1
Promegestone / pharmacology
RNA, Messenger / analysis
Receptors, Calcitriol / genetics
Receptors, Cytoplasmic and Nuclear / genetics*
Receptors, Retinoic Acid / genetics
Receptors, Steroid / genetics
Repressor Proteins / genetics
Reverse Transcriptase Polymerase Chain Reaction
Silencer Elements, Transcriptional
Transcription Factors
Tumor Cells, Cultured
p300-CBP Transcription Factors
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclic AMP Response Element-Binding Protein; 0/NCOR1 protein, human; 0/Nuclear Proteins; 0/Nuclear Receptor Co-Repressor 1; 0/RNA, Messenger; 0/Receptors, Calcitriol; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Retinoic Acid; 0/Receptors, Steroid; 0/Repressor Proteins; 0/Transcription Factors; 11061-68-0/Insulin; 34184-77-5/Promegestone; 50-28-2/Estradiol; EC 2.3.1.-/Acetyltransferases; EC 2.3.1.48/Histone Acetyltransferases; EC 2.3.1.48/p300-CBP Transcription Factors; EC 2.3.1.48/p300-CBP-associated factor

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