ER-α36, a Variant of ER-α, Promotes Tamoxifen Agonist Action in Endometrial Cancer Cells via the MAPK/ERK and PI3K/Akt Pathways

Background Recently, a novel variant of ER-α, ER-α36 was identified and cloned. ER-α36 lacks intrinsic transcription activity and mainly mediates nongenomic estrogen signaling. Here, we studied the role of nongenomic estrogen signaling pathways mediated by ER-α36 in tamoxifen resistance and agonist...

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Published in:PloS one 2010-02, Vol.5 (2), p.e9013
Main Authors: Lin, Sheng-Li, Yan, Li-Ying, Zhang, Xin-Tian, Yuan, Ju, Li, Mo, Qiao, Jie, Wang, Zhao-Yi, Sun, Qing-Yuan
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Amino acids
Biology
Breast cancer
c-Myc protein
Cancer
Cell Biology/Cell Signaling
Cell cycle
Endocrine therapy
Endometrial cancer
Endometrium
Enzyme inhibitors
Estrogen
Estrogen receptors
Estrogens
Extracellular signal-regulated kinase
Genes
Growth factors
Gynecology
Immunoblotting
Immunofluorescence
Immunology
Kinases
Laboratories
Ligands
Localization
MAP kinase
Metastasis
Myc protein
Obstetrics
Oncology/Breast Cancer
Oncology/Gynecological Cancers
Pathways
Phosphorylation
Plasma
Proteins
Reproductive health
Signal transduction
Signaling
siRNA
Tamoxifen
Transcription
Tumors
Uterine cancer
Zoology
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Summary:Background Recently, a novel variant of ER-α, ER-α36 was identified and cloned. ER-α36 lacks intrinsic transcription activity and mainly mediates nongenomic estrogen signaling. Here, we studied the role of nongenomic estrogen signaling pathways mediated by ER-α36 in tamoxifen resistance and agonist action. Methodology The cellular localization of ER-α36 was examined by immunofluorescence in MCF-7 cells and Hec1A cells. MCF-7 breast cancer cells, MCF-7 cells expressing recombinant ER-α36 (MCF-7/ER36), Hec1A endometrial cancer cells and Hec1A cells with siRNA knockdown of ER-α36 (Hec1A/RNAiER36) were treated with 17β-estradial (E2) and tamoxifen (TAM) in the absence and presence of kinase inhibitor U0126 and LY294002. We examined phosphorylation of signaling molecules and the expression of c-Myc by immunoblotting, and tumor cell growth by MTT assay. Conclusions ER variant ER-α36 enhances TAM agonist activity through activation of the membrane-initiated signaling pathways in endometrial cancer, and that ER-α36 is involved in de novo and acquired TAM resistance in breast cancer.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0009013