Estrogen Induces c-myc Transcription by Binding to Upstream ERE Element in Promoter

Abstract

Estrogen Receptor α(ERα) is reported to regulate the expression of many target genes by binding to specific estrogen response elements (EREs) in their promoters. c-myc is known to be over-expressed in most of the human carcinomas due to dysregulated transcription, translation, or protein stability. Estrogen (E) can induce the c-myc expression by binding to an upstream enhancer element in its promoter. This suggests that elevated estradiol (E2), a potent form of estrogen, levels could induce the expression of c-myc in breast cancer (BC). The expression of c-myc and estradiol were induced at Stage III and Stage IV of breast cancer. c-myc and estradiol expression was also associated with the established risk factors of breast cancer, such as BMI. Age at the time of the disease was alsocorrelated with the relative expression of c-myc and estradiol (p < 0.0007 and p < 0.000001). The correlation coefficient (R = 0.462) shows a positive relationship between estradiol bound ER, ER, and c-myc. Docking energy −229 kJ/mol suggests the binding affinity of estradiol bound ER binding to 500 bp upstream of proximal promotor of c-myc at three distinct positions. The data presented in this study proposed that the expression of c-myc and estradiol are directly correlated in breast cancer. The prognostic utility of an induced level of c-myc associated with the normal status of the c-myc gene and estradiol for patients with metastatic carcinoma should be explored further.