Abstract
The involvement of the coxsackie and adenovirus receptor (CAR), an adhesion molecule known to be the main determinant of adenovirus transduction of the cells, in cancer is currently under investigation. Recent reports suggest that CAR levels are elevated in breast cancer, and this may have an impact on its use as means of delivery for gene therapy. In this study, we show that estradiol (E(2)) treatment of the estrogen receptor (ER)-positive breast cancer cell MCF-7 increases CAR levels and, in turn, enhances adenoviral transduction. Employing the transfection of CAR promoters in breast cancer cells, we show that this regulation of CAR expression occurs at the transcriptional level. In addition, and by chromatin immunoprecipitation, we have identified a crucial region of CAR promoter that controls E(2) responsiveness of CAR gene through the recruitment of ER. Moreover, utilizing CAR antibodies or CAR silencing by RNA interference repressed the estrogen-dependent growth of breast cancer cells, whereas the stable expression of CAR in MCF-7 or MDA-MB-231 cells led to an increased proliferation. Altogether, our data suggest that CAR is a novel estrogen-responsive gene, which is involved in the E(2)-dependent proliferation of breast cancer cells.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology*
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Adenoviruses, Human / physiology
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Antibodies, Monoclonal / pharmacology
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology*
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Cell Division / drug effects
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Cell Line, Tumor / drug effects
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Cell Line, Tumor / metabolism
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Coxsackie and Adenovirus Receptor-Like Membrane Protein
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Estradiol / pharmacology*
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Estrogen Receptor alpha / drug effects
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Estrogen Receptor alpha / genetics
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Estrogens / physiology*
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Female
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Genes, Reporter
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Humans
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Mutagenesis, Site-Directed
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / drug effects
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / pathology*
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Promoter Regions, Genetic / drug effects
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RNA Interference
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RNA, Neoplasm / biosynthesis
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RNA, Small Interfering / pharmacology
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Receptors, Virus / antagonists & inhibitors
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Receptors, Virus / drug effects
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Receptors, Virus / genetics
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Receptors, Virus / physiology*
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Recombinant Fusion Proteins / physiology
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Signal Transduction
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Transcription, Genetic
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Transfection
Substances
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Antibodies, Monoclonal
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CLMP protein, human
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Coxsackie and Adenovirus Receptor-Like Membrane Protein
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ESR1 protein, human
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Estrogen Receptor alpha
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Estrogens
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Neoplasm Proteins
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RNA, Neoplasm
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RNA, Small Interfering
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Receptors, Virus
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Recombinant Fusion Proteins
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Estradiol