Modeling cell cycle control and cancer with pRB tumor suppressor.
Cancer is a complex syndrome of diseases characterized by the increased abundance of cells that disrupts the normal tissue architecture within an organism. Defining one universal mechanism underlying cancer with the hope of designing a magic bullet against cancer is impossible, largely because there is so much variation between various types of cancer and different individuals. However, we have learned much in past decades about different journeys that a normal cell takes to become cancerous, and that the delicate balance between oncogenes and tumor suppressor is upset, favoring growth and survival of the tumor cell. One of the most important cellular barriers to cancer development is the retinoblastoma tumor suppressor (pRB) pathway, which is inactivated in a wide range of human tumors and controls cell cycle progression via repression of the E2F/DP transcription factor family. Much of the clarity with which we view tumor suppression via pRB is due to our belief in the universality of the cell cycle and our attempts to model tumor pathways in vivo, nowhere so evident as in the multitude of data emerging from mutant mouse models that have been engineered to understand how cell cycle regulators limit growth in vivo and how deregulation of these regulators facilitates cancer development. In spite of this clarity, we have witnessed with incredulity several stunning results in the last 2 years that have challenged the very foundations of the cell cycle paradigm and made us question seriously how important these cell cycle regulators actually are.
Yamasaki
Lili
L
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
D000818:Animals; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D006801:Humans; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins