Open AccessJournal Article
Expression of a constitutively active estrogen receptor variant in the estrogen receptor-negative BT-20 human breast cancer cell line.
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TLDR
The presence of this ER variant in breast tumor cell lines, as well as breast tumor biopsies and uterine tissue, suggests that it is a naturally occurring variant that may arise by alternative splicing, and whose overexpression may be involved in the progression of breast tumors to a hormone-independent state.Abstract:
Estrogen receptor (ER) expression by breast tumors is an important predictor of disease-free survival in breast cancer patients and, more importantly, is a strong predictor of response to endocrine therapy. Variant forms of the ER may play an important role in the loss of hormone responsiveness and the progression to hormone independence. We have examined a panel of human breast tumor cell lines, both ER-positive and ER-negative, and have identified an ER mRNA variant containing a deletion of exon 5 in the ER-negative BT-20 and ER-positive MCF-7 cell lines. This exon 5 deletion variant has been previously reported to be overexpressed in ER-negative/progesterone receptor-positive breast tumors. Using RNase protection analysis, we have found that the predominant ER transcript in the BT-20 cells is the exon 5 deletion variant, while the principal transcript in MCF-7 cells is the wild-type ER mRNA. The variant ER transcript is translated into a truncated receptor protein of approximately M(r) 42,000 when expressed in yeast and, more important, in breast tumor cells. This is the first demonstration of an exon 5 deletion variant ER protein. Functional analysis has shown that this variant ER possesses constitutive transcriptional regulatory activity with respect to an estrogen-regulated reporter gene construct in a yeast expression system. The presence of this ER variant in breast tumor cell lines, as well as breast tumor biopsies and uterine tissue, suggests that it is a naturally occurring variant that may arise by alternative splicing, and whose overexpression may be involved in the progression of breast tumors to a hormone-independent state.read more
Citations
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The different roles of ER subtypes in cancer biology and therapy
TL;DR: The changes in the bioavailability of ERs in tumours promote the selective restoration of their activity as one of the major therapeutic approaches for hormone-dependent cancers.
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Estrogen receptor mutations in human disease.
TL;DR: A review of naturally occurring splice variants of both ERalpha and ERbeta alterations in breast cancer and the mechanism of action is outlined.
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Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy.
TL;DR: Analysis of recurrent tumor samples may improve the predictive value of ER and PR assays, and loss of ER expression in recurrent breast cancer should be considered as a cause for poor response to endocrine therapy in primarily ER-positive patients.
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Differential expression of CYP1A1 and CYP1B1 in human breast epithelial cells and breast tumor cells.
David C. Spink,Barbara C. Spink,J. Q. Cao,J. A. Depasquale,Brian T. Pentecost,M. J. Fasco,Ying Li,Thomas R. Sutter +7 more
TL;DR: The results show that breast epithelial cells and tumor cells vary widely with regard to AhR-mediated CYP1A1 and CYP 1B1 induction, suggesting that factors in addition to the AhR regulate CYP2A2 and CYp1B1 gene expression.
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Androgens induce divergent proliferative responses in human breast cancer cell lines
Stephen N. Birrell,Jacqueline M. Bentel,Theresa E. Hickey,Carmela Ricciardelli,M.A. Weger,David J. Horsfall,Wayne D. Tilley +6 more
TL;DR: The results suggest that androgen action in breast cancer cell lines may not be solely mediated by binding of androgen to the AR and metabolites of DHT with oestrogenic activity, or androgen binding to receptors other than the AR, may explain the divergent responses to androgens observed in different breast cancercell lines.
References
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Journal Article
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Supercoil sequencing: a fast and simple method for sequencing plasmid DNA
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TL;DR: A method for obtaining sequence information directly from plasmid DNA is presented, and the advantages include speed, simplicity, avoidance of additional cloning steps into single-stranded phage M13 vectors, and hence applicability to sequencing large numbers of samples.
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