Antiestrogen action and growth factor regulation.
The basis of the anti-proliferative action of antiestrogens is generally considered to be their ability to inhibit estrogen induced growth pathways by competitively inhibiting the binding of estrogen to the estrogen receptor. Recent data suggest that this may not be the entire story. Moreover, the cascade of events responsible for inhibition of mitogenesis after an initial interaction with the estrogen receptor is poorly understood. Multiple growth factor pathways operate in both normal and neoplastic estrogen/antiestrogen target tissues. While it is unlikely that any single pathway is pivotal, interactions of estrogen and/or antiestrogens with some of these pathways have been implicated in their proliferative effects. The exact molecular mechanisms remain unclear but autocrine, paracrine/juxtacrine, intracrine, and endocrine mediators or various combinations of them are likely to be involved in vivo. Super-imposed on this is the possibility that 'cross-talk' between intracellular signaling pathways may also be involved. Elucidation of such molecular mechanisms will be important with respect to design of novel antiestrogenic/antimitogenic drugs and alternative treatment strategies for both breast and uterine cancer.
Murphy
L C
LC
Dept of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000473:pathology / Q000503:physiopathology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006131:Growth Inhibitors / Q000502:physiology; D006133:Growth Substances / Q000096:biosynthesis / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000166:cytology / Q000502:physiology
D004965:Estrogen Antagonists; D004967:Estrogens; D006131:Growth Inhibitors; D006133:Growth Substances; D011960:Receptors, Estrogen