Crossroads of estrogen receptor and NF-kappaB signaling.
Cellular homeostasis in higher organisms is maintained by balancing cell growth, differentiation, and death. Two important systems that transmit extracellular signals into the machinery of the cell nucleus are the signaling pathways that activate nuclear factor kappaB (NF-kappaB) and estrogen receptor (ER). These two transcription factors induce expression of genes that control cell fates, including proliferation and cell death (apoptosis). However, ER has anti-inflammatory effects, whereas activated NF-kappaB initiates and maintains cellular inflammatory responses. Recent investigations elucidated a nonclassical and nongenomic effect of ER: inhibition of NF-kappaB activation and the inflammatory response. In breast cancer, antiestrogen therapy might cause reactivation of NF-kappaB, potentially rerouting a proliferative signal to breast cancer cells and contributing to hormone resistance. Thus, ER ligands that selectively block NF-kappaB activation could provide specific potential therapy for hormone-resistant ER-positive breast cancers.
Biswas
Debajit K
DK
Department of Cancer Biology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Debajit_Biswas@dfci.harvard.edu
Singh
Sindhu
S
Shi
Qian
Q
Pardee
Arthur B
AB
Iglehart
J Dirk
JD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects; D019938:Cyclin D1 / Q000502:physiology; D004967:Estrogens / Q000819:agonists / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000502:physiology; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000172:deficiency / Q000187:drug effects / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004967:Estrogens; D020672:I-kappa B Proteins; D008024:Ligands; D016328:NF-kappa B; D011720:Pyrazoles; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; C499198:WAY-169916; D019938:Cyclin D1