Table 1 Table summarizes estrogens associated regulatory molecules and their respective pathways delivering important physiological functions associated to breast cancer risk and initiating or promoting breast cancer
Mode of action of E2 | Binding location | Regulated genes and pathways | Physiological function | Breast cancer risk |
|---|---|---|---|---|
Genomic (direct)  E2 + nuclear ER | Hormone response element on target gene | JUN, FOS, PGR, TP53, HRAS, Bcl2, BRCA1, CHAT, NQO1, CKB, LTF, SCGB1A1 | Stress activated kinase, glucose homeostasis, cell growth and tissue development | These receptors, genes and pathways are associated to various cell growth associated functions The imbalances among these pathways may initiate or promote or support cancer |
Genomic indirect  E2 + nuclear ER | AP-1 (Jun/FOS) SP1 C-Rel subunit of Nfκβ ATF-2/C-Jun ATF-2/cAMP CREB JAK/STAT SRE ATF1/CREP Nuclear transcription factor Y | IGF-1, ovalbumin, cyclin D1 Retinoic acid-R 1α gene, LDL-R gene, eNOS, cfos, cyclin D1 Inhibits Nfκβ mediated expression of IL-6, inhibits cytokine IL-6 Cyclin-D1 Bcl2 gene E2F1 gene | Progression of cells through G1 phase of cell cycle Progression of cells through G1 phase of cell cycle Role in cytokine receptor signalling Anti-apoptotic | |
Non-genomic  E2 + ER | IGF-1 EGF G-protein SRC MMP | ERK P38/MAPK P13K/AKT PLC/PKC cAMP/PKA | Promotes G1-S promotes survival signal, enhances antiapoptotic Caspase3 eNOS activation-release NO |