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

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 signal...

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Main Authors: Qihong Li, Haiyan Sun, Jingcai Zou, Cheng Ge, Kaitao Yu, Yuan Cao, Quan Hong
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2013-06-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/350101
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author Qihong Li
Haiyan Sun
Jingcai Zou
Cheng Ge
Kaitao Yu
Yuan Cao
Quan Hong
author_facet Qihong Li
Haiyan Sun
Jingcai Zou
Cheng Ge
Kaitao Yu
Yuan Cao
Quan Hong
author_sort Qihong Li
collection DOAJ
description 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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spelling doaj.art-b7a07823501049929ab6ca5e514f54082022-12-21T19:12:43ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782013-06-0131683384110.1159/000350101350101Increased Expression of Estrogen Receptor α-36 by Breast Cancer Oncogene IKKε Promotes Growth of ER-Negative Breast Cancer CellsQihong LiHaiyan SunJingcai ZouCheng GeKaitao YuYuan CaoQuan HongBackground/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.http://www.karger.com/Article/FullText/350101IKKεER-α36ER-negative breast cancer
spellingShingle Qihong Li
Haiyan Sun
Jingcai Zou
Cheng Ge
Kaitao Yu
Yuan Cao
Quan Hong
Increased Expression of Estrogen Receptor α-36 by Breast Cancer Oncogene IKKε Promotes Growth of ER-Negative Breast Cancer Cells
Cellular Physiology and Biochemistry
IKKε
ER-α36
ER-negative breast cancer
title Increased Expression of Estrogen Receptor α-36 by Breast Cancer Oncogene IKKε Promotes Growth of ER-Negative Breast Cancer Cells
title_full Increased Expression of Estrogen Receptor α-36 by Breast Cancer Oncogene IKKε Promotes Growth of ER-Negative Breast Cancer Cells
title_fullStr Increased Expression of Estrogen Receptor α-36 by Breast Cancer Oncogene IKKε Promotes Growth of ER-Negative Breast Cancer Cells
title_full_unstemmed Increased Expression of Estrogen Receptor α-36 by Breast Cancer Oncogene IKKε Promotes Growth of ER-Negative Breast Cancer Cells
title_short Increased Expression of Estrogen Receptor α-36 by Breast Cancer Oncogene IKKε Promotes Growth of ER-Negative Breast Cancer Cells
title_sort increased expression of estrogen receptor α 36 by breast cancer oncogene ikkε promotes growth of er negative breast cancer cells
topic IKKε
ER-α36
ER-negative breast cancer
url http://www.karger.com/Article/FullText/350101
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