Functional domains of the human estrogen receptor

Kumar, Vijay; Green, Stephen; Stack, Gary; Berry, Meera; Jin, Jia-Rui; Chambon, Pierre

doi:10.1016/0092-8674(87)90581-2

Cited by 1,228 publications

(620 citation statements)

References 39 publications

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“…30). A negative feedback, by binding and competition of free receptors to ERE when the E, concentration becomes too small, may be involved as it has been shown that free receptors can bind ERE without gene transcription activation (Kumar et al, 1987). Nevertheless, our results are different from those described in Xenopus (Barton and Shapiro, 1988).…”

Section: Discussioncontrasting

confidence: 91%

In vivo estrogen induction of hepatic estrogen receptor mRNA and correlation with vitellogenin mRNA in rainbow trout

Pakdel

Féon

Gac

et al. 1991

Molecular and Cellular Endocrinology

160

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SummaryWe have previously described the cloning, sequencing and in vitro expression of a full-length rainbow trout estrogen receptor cDNA (rtER cDNA). This full cDNA randomly labelled was used to study the estrogen induction of hepatic rtER mRNA in correlation with vitellogenin (Vg) mRNA in different physiolo~cal situations.In this paper, we show that in the liver two mRNA species are under hormonal control and their level increases about g-fold after estrogen stimulation.These two mRNAs are expressed and induced in the liver as early as the hatching stage in correlation with the expression of Vg mRNA. A long-term analysis of rtER mRNA after estradiol (E2) injection shows a transient induction of the nuclear ER and its mRNA which recover to the basal level after 2 weeks. Nevertheless, a memory effect was observed on the expression of the Vg gene which does not appear to be directly related to the estrogen receptor level.

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Section: Discussioncontrasting

confidence: 91%

In vivo estrogen induction of hepatic estrogen receptor mRNA and correlation with vitellogenin mRNA in rainbow trout

Pakdel

Féon

Gac

et al. 1991

Molecular and Cellular Endocrinology

160

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“…HEA5 is truncated at amino acid 365 in ER and would be expected to act through AF-1 in a constitutive manner. We compared the transactivational ability of HEA5 with ER (HEGO) and with the in vitro generated mutant HE15 [containing amino acids 1-281 of ER (Kumar et al, 1987], which activates transcription through AF-1 (Tora et al, 1989a). The constructs used and the extent of the deletions are shown in Figure 5A.…”

Section: Transcriptional Activation By Hea5 In Mammalian Cellsmentioning

confidence: 99%

“…Alignment of the predicted ER amino acid sequences from different species shows that it can be divided into six regions A to F on the basis of differing amino acid sequence homology . Functional studies have shown that region C encodes the DNA-binding domain (DBD) and region E contains the hormone-binding domain (HBD) Kumar et al, 1987). Regions A/B and E contain trans-activation functions 1 (AFI) and 2 (AF-2) respectively (Kumar et al, , 1987Webster et al, 1988;Lees et al, 1989;Tora et al, 1989a;Berry et al, 1990).…”

mentioning

confidence: 99%

“…Functional studies have shown that region C encodes the DNA-binding domain (DBD) and region E contains the hormone-binding domain (HBD) Kumar et al, 1987). Regions A/B and E contain trans-activation functions 1 (AFI) and 2 (AF-2) respectively (Kumar et al, , 1987Webster et al, 1988;Lees et al, 1989;Tora et al, 1989a;Berry et al, 1990). Recent studies indicate that region F plays a role in modulating transcriptional activation by ER (Montano et al, 1995).…”

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confidence: 99%

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Presence of exon 5-deleted oestrogen receptor in human breast cancer: functional analysis and clinical significance

Desai

Luqmani²,

Walters³

et al. 1997

Br J Cancer

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Summary A variant form of the human oestrogen receptor (ER) mRNA lacking sequences encoded within exon 5 has been described (Fuqua SAW, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, Nawaz Z, O'Malloy BW, McGuire WL 1991, Cancer Res 51: 105-1 09).We have examined the expression of the exon 5-deleted ER (HEA5) mRNA variant in breast biopsies using reverse transcriptase polymerase chain reaction (RT -PCR). HEA5 mRNA was present in only 13% of non-malignant breast tissues compared with 32% of carcinomas (95% Cl, P=0.05). Presence of the HEA5 mRNA was associated with the presence of immunohistochemically detected ER (P=0.015) and progesterone receptor (PR) (P=0.02). There was a positive correlation between the presence of HEA5 and disease-free survival (P=0.05), suggesting that the presence of HEA5 may be an indicator of better prognosis. We have raised a monoclonal antibody specific to the C-terminal amino acids of HEA5. This antibody recognized the variant but not the wild-type ER protein. We show that HEA5 protein is present in breast cancer using immunohistochemical techniques. We also analysed trans-activation by HEA5 in mammalian cells and showed that, in MCF-7 cells, HEA5 competes with wild-type ER to inhibit ERE-dependent trans-activation. Our results indicate that this variant is unlikely to be responsible for endocrine resistance of breast cancer, but its presence at both the mRNA and protein level suggest that it may, nevertheless, be involved in regulating the expression of oestrogen-responsive genes in breast cancer.Keywords: breast neoplasm; exon; polymerase chain reaction; oestrogen receptor; transcription Two-thirds of human breast carcinomas are characterized by the presence of appreciable amounts of oestrogen receptor (ER) protein.A proportion of these tumours also contain progesterone receptor (PR) and it is generally accepted that ER regulates PR gene expression. The presence of ER is correlated with a better prognosis and ER+/PR+ tumours are much more likely to respond to endocrine therapy than ER-/PR-tumours. Interestingly, ER-/PR+ tumours are twice as likely to respond as ER+/PR-tumours. A significant proportion of ER+/PR+ tumours, however, fail to respond to endocrine therapy and those that do so eventually become resistant to such therapy. The mechanisms leading to endocrine resistance are not yet clear (for reviews see McGuire, 1978;McGuire et al, 1991;Fuqua, 1994;Horwitz, 1994;Sluyser, 1994).The human oestrogen receptor cDNA and its gene (Ponglikitmongkol et al, 1988) have been cloned and the molecular mechanisms by which it acts are well understood. Alignment of the predicted ER amino acid sequences from different species shows that it can be divided into six regions A to F on the basis of differing amino acid sequence homology . Functional studies have shown that region C encodes the DNA- Kumar et al, 1987). Regions A/B and E contain trans-activation functions 1 (AFI) and 2 (AF-2) respectively (Kumar et al, , 1987Webster et al, 1988; Lees et al, 1989; Tora et al, 1989a;Berry et ...

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“…However, E 2 stimulated CAT activity in transformed KwtER cells at a level similar to that seen in non-transformed Kwt or ER cells. ER has two transcriptional activation domains, AF1 and AF2, which are located in the NH2-terminal A/B region and in the ligand-binding region E, respectively (Kumar et al, 1987). The signal through membraneassociated receptor tyrosine kinase-Ras-Raf-MAPK enhances the activity of ER-AF1 by stimulating phosphorylation of the serine residue at codon 118 (Kato et al, 1995).…”

Section: Er Contributes To Nih3t3 Cell Transformationmentioning

confidence: 99%

Contribution of enhanced transcriptional activation by ER to [12Val] K-Ras mediated NIH3T3 cell transformation

et al. 1997

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We investigated the biological signi®cance of estrogen receptors (ER) in NIH3T3 cell transformation by the [ 12 Val] K-Ras mutant. This mutant enhanced the steady state level of ER. Cells expressing mutant K-Ras (K12V cell) were tumorigenic. To determine the role of ER accumulation in Ras-transformed cells, we developed cells (KwtER cells) that overexpressed both wild-type (wt) K-Ras and ER, and found these cells were also tumorigenic. E 2 stimulated the transcriptional activity by ER dominantly in K12V cells. However, only partial activation of ER by E 2 was seen in KwtER cells. In the presence of 10% serum in media, the activation of ER appeared only in transformed KtwER and K12V cells, suggesting that two independently transmitted signals, the E 2 -ER binding and the ER-AF1 activation, are necessary for ER activation and that the dominant activation of ER might be involved in Ras-mediated cell transformation. Co-expression of progesterone receptor (PR) with mutant K-Ras led to suppression of tumorigenicity and inhibition of the activation of ER. The antisense oligomers complementary to the ER suppressed proliferation and transformed phenotypes of K12V cells. These observations support the importance of ER in Ras-mediated cell transformation.

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Functional domains of the human estrogen receptor

Cited by 1,228 publications

References 39 publications

In vivo estrogen induction of hepatic estrogen receptor mRNA and correlation with vitellogenin mRNA in rainbow trout

In vivo estrogen induction of hepatic estrogen receptor mRNA and correlation with vitellogenin mRNA in rainbow trout

Presence of exon 5-deleted oestrogen receptor in human breast cancer: functional analysis and clinical significance

Contribution of enhanced transcriptional activation by ER to [12Val] K-Ras mediated NIH3T3 cell transformation

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