Expression of ER-α36, a Novel Variant of Estrogen Receptor α, and Resistance to Tamoxifen Treatment in Breast Cancer

Shi, Liang; Dong, Bin; Li, Zhongwu; LU, Yunwei; Ouyang, Tao; Liu, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Wang, Zhaoyi; Xie, Yuntao

doi:10.1200/jco.2008.17.2254

Cited by 197 publications

(136 citation statements)

References 27 publications

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“…The activity of the NFκB signaling cascade is associated with mammary carcinogenesis, especially tumors with an aggressive and ERnegative phenotype [9]. ER-α36 expression is regulated differently from ER-α66, consistent with the findings that ER-α36 is expressed in specimens from ER-negative breast cancer patients and established ER-negative breast cancer cells that lack ER-α66 expression [10,11]. Although the function of ER-α36 has been studied in cancer, to our knowledge, it has not yet been known in the nervous system.…”

Section: Introductionsupporting

confidence: 74%

Estrogen Receptor Alpha 36 Gene Knockdown Promote the Expression of NF-κB in PC12 Cells

Zou¹,

Qu²,

Xu³

et al. 2013

OJEMD

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The nuclear transcription factors κB (NF-κB) is widely existed in various kinds of cell types in the nervous system and plays an important role in neuron apoptosis and neurodegenerative diseases. Estrogen receptor alpha 36 (ER-α36) is a novel variant of ERα (as known ER-α66) which can transduce both estrogen-and antiestrogen-dependent activation of MAPK signal pathway and stimulate cell growth. Here, we aimed to detect the effect of ER-α36 gene silencing on the expression of NF-κB in normal cultured PC12 cells and to provide an experimental foundation for understanding the function of ER-α36 in nerve cells. PC12 cells with ER-α36 expression knocked down by the shRNA method. Then Western blot and immunocytochemical staining were performed to detect the expression and translocation of NF-κB after transfection. The results showed that NF-κB expression was significantly higher comparing with the control group after transfection (P < 0.01). Also, NF-κB subunit entered nuclear after transfection; Immunofluorescence staining and immunocytochemical staining of PC12 cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and on the cell nucleus membrane. These data indicate that ER-α36 gene silencing can increase the expression of NF-κB and promote its nuclear translocation in PC12 cells.

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Section: Introductionsupporting

confidence: 74%

Estrogen Receptor Alpha 36 Gene Knockdown Promote the Expression of NF-κB in PC12 Cells

Zou¹,

Qu²,

Xu³

et al. 2013

OJEMD

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“…Approximately 70% of breast cancer cases are ERα-positive, and the remaining 30% are ER-negative [10]. ERα-36 is a variant of conventional ERα, which lacks both transcriptional activation domains of ERα-66, retains DNA-binding domain, partial dimerization and ligand-binding domains, and possesses a unique 27 amino acid domain that replaces the last 138 amino acid of ERα-66 [11,13]. It was found that ERα-36 expression levels were higher in ERnegative tumors and lower in ER-positive tumors [12].…”

Section: Discussionmentioning

confidence: 99%

“…ERα-36 was expressed in ER-negative tumor samples and ER-negative breast cancer cell lines [14]. Some studies have suggested that ERα-36 is involved in nongenomic estrogen signaling, and ERα-36 promotes cell proliferation via the MAPK/ERK pathway in ER-negative breast cancers [13,14]. …”

Section: Introductionmentioning

confidence: 99%

“…Although significant progress has been made in the development of endocrine therapies that target estrogen or ER for ER-positive tumors, there is no effective therapy for the 30% of breast cancers that are ER negative [9,10]. Recently, a 36-kDa variant of ERα-66, named ER-a36 has been identified, it is mainly expressed in the cytoplasm and plasma membrane and has minimal or no nuclear expression in breast cancer cells [11,12,13]. ERα-36 was expressed in ER-negative tumor samples and ER-negative breast cancer cell lines [14].…”

Section: Introductionmentioning

confidence: 99%

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Increased Expression of Estrogen Receptor a-36 by Breast Cancer Oncogene IKKe Promotes Growth of ER-Negative Breast Cancer Cells

Sun

Zou

et al. 2013

Cell Physiol Biochem

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Background/Aims: The expression of estrogen receptor-α (ERα) is one of the most important diagnostic and prognostic factors of breast cancer. Recently, ERα-36 has been identified as a novel variant of ER-α. ERα-36 lacks intrinsic transcription activity and mainly mediates non-genomic estrogen signaling. The noncanonical IKK family member IKKε is essential for regulating antiviral signaling pathways and is recently discovered as a breast cancer oncogene. IKKε interacts with and phosphorylates ERα on serine 167, induces ERα transactivation activity and enhances ERα binding to DNA in ER-positive breast cancer cells. However, the correlation between IKKε and the ERα-36 signaling pathway in ER-negative breast cancer cells remains unclear. Methods and Results: In this study, we show that IKKε interacts with ERα-36 and increases its expression in breast cancer cells. As shown by western blot assays, the upregulation of ERα-36 by IKKε was significant. In MDA-MB-231 cells which are ER-negative, IKKε was able to increase the expression of ERα-36 in a dose-dependent manner, and the RNA interference assay indicated the correlation between IKKε and ERα-36 expression. Moreover, IKKε enhanced the growth of MDA-MB-231 and MDA-MB-436 cells. Conclusions: These results suggest that IKKε increases ERα-36 expression and is involved in ERα-36 mediated non-genomic estrogen signaling.

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“…For example, expression of the variant ER-α36 affects estrogen signaling and is associated with tamoxifen resistance in breast cancer [45] . In addition, the localization of ER variants in breast cancer cells reportedly differs from that of wild type ER [42,46] .…”

Section: The Role Of Er Variants In Cancer Cellsmentioning

confidence: 99%

Estrogen receptors as the novel therapeutic biomarker in non-small cell lung cancer

Kawai

2014

WJCO

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Although a wide range of studies have addressed the relationship between estrogen receptor (ER) expression and prognosis in non-small cell lung cancer (NSCLC), that relationship remains controversial. This is in large part because there is no consensus on the rate of ER expression in NSCLC or on the intracellular distribution of ER expression. This suggests that establishing the relationship between ER expression and prognosis will require standardization of the antibodies used as well as the definition of a positive response. For example, it is supposed from previous studies that ERs in the cytoplasm and nucleus have different relationships to prognosis than ERs in the cytoplasm. Moreover, ER signaling in NSCLC is known to be affected by aromatase, progesterone receptor and epidermal growth factor receptor mutation. However, there has been little functional analysis these mutants and subtypes. This review will focus on what is known about the role of ERs in NSCLC and whether ER can be a useful prognostic marker or therapeutic target in NSCLC.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Estrogen receptor; Non-small cell lung cancer; Epidermal growth factor receptor; Fulvestrant; Combined therapy Core tip: Although there were many studies regarding the role of estrogen receptor (ER) in non-small cell lung cancer (NSCLC), the rate of ER expression or the intracellular distribution of ER remains controversial. This suggests that establishing the relationship between ER expression and prognosis will require standardization of the antibodies used as well as the definition of a positive response. Furthermore, there has been little functional analysis for ER variants. This review will focus on what is known about the role of ERs in NSCLC and whether ER can be a useful prognostic marker or therapeutic target in NSCLC.Kawai H. Estrogen receptors as the novel therapeutic biomarker in non-small cell lung cancer.

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Expression of ER-α36, a Novel Variant of Estrogen Receptor α, and Resistance to Tamoxifen Treatment in Breast Cancer

Cited by 197 publications

References 27 publications

Estrogen Receptor Alpha 36 Gene Knockdown Promote the Expression of NF-κB in PC12 Cells

Estrogen Receptor Alpha 36 Gene Knockdown Promote the Expression of NF-κB in PC12 Cells

Increased Expression of Estrogen Receptor a-36 by Breast Cancer Oncogene IKKe Promotes Growth of ER-Negative Breast Cancer Cells

Estrogen receptors as the novel therapeutic biomarker in non-small cell lung cancer

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