Oestrogen receptor B-region polymorphism and spontaneous abortion in women with breast cancer

Lehrer, Steven; Song, Hee Kyung; Levine, Erica; Dalton, Jack; Savoretti, Penny; Schachter, Beth S.; Sanchez, M.; Thung, SwanN.

doi:10.1016/0140-6736(90)90410-7

Cited by 101 publications

(32 citation statements)

References 19 publications

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“…Researchers have attempted to demonstrate an association between ESR gene polymorphisms and abortion. In 1990, two nearby mutations that led to a silent mutation in codon 87 were associated with spontaneous abortion in women with breast cancer [Lehrer et al 1990]. However, subsequent studies contradicted these findings [Berkowitz et al 1994;Taylor et al 1993].…”

Section: Introductionmentioning

confidence: 52%

The ESR1 gene in unexplained recurrent spontaneous abortion

Pan¹,

Suo²,

Liu³

et al. 2014

Systems Biology in Reproductive Medicine

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Recurrent spontaneous abortion (RSA) is a health problem that affects nearly 1% of fertile couples. However, the underlying etiology and mechanism(s) remain elusive. The aim of this study was to investigate estrogen receptor (ESR) 1 gene polymorphisms for risk association of unexplained recurrent spontaneous abortion (URSA) in the Chinese Han population. The entire coding region of the ESR1 gene was sequenced from 129 URSA patients and 183 healthy controls. There was a significant difference between the G allele and GG genotype distributions, of the ESR1 gene (XbaI) polymorphism, between the URSA and the control groups ( 2 ¼ 14.93, df ¼ 1, p50.001, OR ¼ 2.01 95% CI: 1.41-2.88 by allele; 2 ¼ 12.24, df ¼ 2, p ¼ 0.002 by genotype). The PvuII polymorphism, C allele frequency was higher in RSA than in controls (41.9% vs. 34.7%, respectively). Women carrying C-G haplotype were associated with an increased risk of URSA in this population (permutation test p value ¼ 0.016, OR ¼ 1.76 95% CI: 1.19-2.59). Estrogen receptor 1 gene PvuII and XbaI polymorphisms were associated with URSA in a Chinese Han population. However, independent replication of these associations are necessary to assure veracity.

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Section: Introductionmentioning

confidence: 52%

The ESR1 gene in unexplained recurrent spontaneous abortion

Pan¹,

Suo²,

Liu³

et al. 2014

Systems Biology in Reproductive Medicine

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“…In a previous report, reduced ERα expression caused by a single-nucleotide polymorphism was implicated in the pathogenesis of spontaneous abortion (Lehrer et al 1990). Furthermore, a woman with prior preeclampsia also showed reduced risk of breast cancer, which is consistent with reduced ER Figure 3 The mRNA and protein levels of SRCs in human placenta according to gestational age.…”

Section: Figurementioning

confidence: 99%

“…For endocrine function, the placenta releases hormones into both the maternal and fetal circulations to affect pregnancy, metabolism, fetal growth, and parturition. The endocrine factors produced by the placenta include estrogen, progesterone, chorionic gonadotropin, placental lactogen, placental growth hormone, and many others (Gude et al 2004, Lehrer et al 1990.…”

Section: Introductionmentioning

confidence: 99%

Interaction of steroid receptor coactivators and estrogen receptors in the human placenta

Kim¹,

Park²,

Lee³

et al. 2016

Journal of Molecular Endocrinology

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Female sex steroid hormones such as estrogen and progesterone have a pivotal role in maintaining pregnancy in human and animals. Especially, estrogen exerts specific effects on the cardiovascular system and angiogenesis, and thus affects significantly on placentation. Although the functions of estrogen have been emphasized during pregnancy, their signaling pathways in the placenta have not been fully understood. In this study, estrogen signaling was evaluated according to gestational age. Human placenta samples were collected and divided into early preterm (n = 10), late preterm (n = 18), and term (n = 20) groups. First, serum estrogen concentration and corticotropinreleasing hormone (CRH) mRNA expression, which is known as gestation clock gene, were increased following gestation age in our experimental condition, as we expected. Next, the expression of estrogen receptors (ERs) and steroid receptor coactivators (SRCs) in the placenta was evaluated. ERα (ESR1) and ERβ (ESR2) were expressed highly at term period compared with early preterm. In addition, SRC family including SRC1, SRC2, and SRC3 was expressed in the human placenta, and the levels of SRC1, SRC2, and SRC3 were increased in the placenta at the late stage of gestation. The interaction of ERs with SRCs was also examined, which was significantly enhanced at term period. In the immunostaining results, it was indicated that ERs and SRCs were all dominantly expressed in syncytiotrophoblast cells. These results suggested that SRC1, SRC2, and SRC3 were expressed and interact with ERs highly at the late stage of gestation, and may amplify the signaling of estrogen in the placenta to maintain pregnancy.

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“…Restriction enzyme polymorphisms and point mutations have been described. A point mutation leading to a single amino acid substitution in region B has been implicated in increased incidence of spontaneous abortions (Lehrer et al, 1990(Lehrer et al, , 1992, although the mechanism of action of this mutant is unclear. A recent report describes a point mutation at codon 157 (region B) leading to a premature stop codon (Smith et al, 1994).…”

mentioning

confidence: 99%

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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Oestrogen receptor B-region polymorphism and spontaneous abortion in women with breast cancer

Cited by 101 publications

References 19 publications

The ESR1 gene in unexplained recurrent spontaneous abortion

The ESR1 gene in unexplained recurrent spontaneous abortion

Interaction of steroid receptor coactivators and estrogen receptors in the human placenta

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

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