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Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Breast Cancer | Primary research

Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκβ interplay

Authors: Aarifa Nazmeen, Guangping Chen, Tamal Kanti Ghosh, Smarajit Maiti

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Estrogen sulfotransferase catalyzes conjugation of sulfuryl-group to estradiol/estrone and regulates E2 availability/activity via estrogen-receptor or non-receptor mediated pathways. Sulfoconjugated estrogen fails to bind estrogen-receptor (ER). High estrogen is a known carcinogen in postmenopausal women. Reports reveal a potential redox-regulation of hSULT1E1/E2-signalling. Further, oxidatively-regulated nuclear-receptor-factor 2 (Nrf2) and NFκβ in relation to hSULT1E1/E2 could be therapeutic-target via cellular redox-modification.

Methods

Here, oxidative stress-regulated SULT1E1-expression was analyzed in human breast carcinoma-tissues and in rat xenografted with human breast-tumor. Tumor and its surrounding tissues were obtained from the district-hospital. Intracellular redox-environment of tumors was screened with some in vitro studies. RT-PCR and western blotting was done for SULT1E1 expression. Immunohistochemistry was performed to analyze SULT1E1/Nrf2/NFκβ localization. Tissue-histoarchitecture/DNA-stability (comet assay) studies were done.

Results

Oxidative-stress induces SULT1E1 via Nrf2/NFκβ cooperatively in tumor-pathogenesis to maintain the required proliferative-state under enriched E2-environment. Higher malondialdehyde/non-protein-soluble-thiol with increased superoxide-dismutase/glutathione-peroxidase/catalase activities was noticed. SULT1E1 expression and E2-level were increased in tumor-tissue compared to their corresponding surrounding-tissues.

Conclusions

It may be concluded that tumors maintain a sustainable oxidative-stress through impaired antioxidants as compared to the surrounding. Liver-tissues from xenografted rat manifested similar E2/antioxidant dysregulations favoring pre-tumorogenic environment.
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Metadata
Title
Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκβ interplay
Authors
Aarifa Nazmeen
Guangping Chen
Tamal Kanti Ghosh
Smarajit Maiti
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-1153-y

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