Rho GTPases as key transducers of proliferative signals in g1 cell cycle regulation.
Mitogenic growth factor- and integrin-dependent signaling pathways cooperate to control the proliferation of nontransformed cells. As integral mediators of these networks, the Rho family of GTPases play a pivotal role in G1 cell cycle progression, primarily through regulation of cyclin D1 expression, as well as the levels of the cyclin-dependent kinase inhibitors p21cip1 and p27kip1. Such dual control of both the critical positive and negative regulators of G1 progression make the Rho GTPases prime candidates to target the autonomous proliferation which typifies cancer cells. Cyclin D1 has been identified as an important oncogene and the cdk inhibitors as tumor suppressors in human breast carcinogenesis. Evidence pointing to the potential role of Rho-dependent pathways and their interaction with oncogenic Ras in contributing to such cell cycle abnormalities that characterize human breast cancer is also presented.
Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL 33136, USA. cwelsh@med.miami.edu
Catherine F
CF
Welsh
D001943:Breast Neoplasms / Q000209:etiology / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D008934:Mitogens / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D008934:Mitogens; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins