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Redox Regulation of Estrogen Signaling in Human Breast Cancer

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Handbook of Oxidative Stress in Cancer: Mechanistic Aspects

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Abstract

Estrogen and oxidative stress are interconnected in a very delicate fashion, leading to redox regulation of estrogen and its regulatory molecules. On the other hand, estrogen regulates the environmental oxidative stress via its intermediate metabolites. Transcription factors such as Nrf2 and nuclear factors such as NFκB intertwined with estrogen and oxidative stress. The current study shapes a possible associative pathway involving NFκB, Nrf2, SULT1E1, estrogen, and oxidative stress to hypothesize possible stimulators and inhibitors and the concerned targets, which may either prevent cancer initiation or be possible therapeutics for late-stage cancer. Cancer cells possess stem cell property, which helps in disease recurrence and tumor resistance. G6PD and HIF-1α were upregulated in MCF-7 and MDA-MB-231 cells by Nrf2 overexpression. HIF-1α coordinates the metabolic adaptation in hypoxic cancer cells. Nrf2 may upregulate GCLC and GSH, which decreases intracellular ROS, leading to a strong reducing environment, which may upregulate nuclear FoxO3a and its binding to the Bmi-1 promoter. Nuclear FoxO3a-mediated transcription is responsible for the self-renewal activity of breast cancer stemlike cells. Our earlier study conferred that estrogen partially regulates MMP and metastasis along with simultaneous regulations of NFκβ, SULT1E1, and Nrf2 via oxidative stress under the influence of estradiol. Overall, these activities of estrogen under redox regulation may contribute to the severity of human breast carcinogenesis.

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Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Cell & Molecular Therapeutics Lab, Oriental Institute of Science and Technology, Midnapore, West Bengal, India

    Aarifa Nazmeen & Smarajit Maiti

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  1. Aarifa Nazmeen
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  2. Smarajit Maiti
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Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA

    Bimal K. Ray

  3. CSIR-Indian Institute of Chemical Biology, Kolkata, India

    Susanta Roychoudhury

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Nazmeen, A., Maiti, S. (2022). Redox Regulation of Estrogen Signaling in Human Breast Cancer. In: Chakraborti, S., Ray, B.K., Roychoudhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-9411-3_85

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