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International Journal of Genetic Modifications and Recombinations Review Article

Deciphering the Roles of Estrogen Receptors and 27-Hydroxycholesterol in BC Progression

  1. Tombin Thomas Geochem Laboratories Private Limited, Aroor

Abstract

Breast cancer (BC) ranks among the top causes of cancer-related deaths in women worldwide. Many risk factors of BC are linked to estrogen. Experiments of Beatson in 1896 show the role of steroid hormones as major determinant in BC. Action of steroid hormones is mediated by their receptors including Estrogen receptors (ERs). ERs are part of a subfamily of ligand-regulated transcription factors. Their primary role is to translate hormone signals into a wide range of physiological responses across different organs. One of the widely studied ER is ER-alpha. One of the major strategies for the treatment of BC is the prevention of the expression of ER-alpha by using antiestrogens, such as tamoxifen and ICI 182,780. The complete understanding of ER-alpha function and inhibition has been gone far by new discoveries of ER-alpha mutations, coregulatory proteins modulating ER activity, alternative downstream signaling pathways, and crosstalk with other intracellular signal transduction pathways. Since hormone therapy based on ER-alpha involves the utilization of antiestrogens and aromatase inhibitors, on other hand 27-hydroxycholesterol (27HC) can bind and activate ERs, which make them supportive to BC. 27HC is synthesized from cholesterol by the enzyme sterol 27-hydroxylase, also known as cytochrome P450 27A1 (CYP27A1). Since the presence 27HC is directly proportional to the presence of cholesterol, their role in obesity associated BC is evident. 27-HC also involved auxiliary targets that facilitate the metastatic phenotype. 27-HC is not engaging in metastasis through ER receptors, instead the act by the activation of the liver X receptors. Amy E. Baek et al. came forward to address this possibility through an experiment with mice. The results of these experiments showed that mice pretreated with 27HC developed significantly more metastatic nodules compared to those pretreated with a placebo.

Keywords

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