title: Modulation of cell cycle components by epigenetic and genetic events.
abstract: Cell cycle progression is monitored by surveillance mechanisms, or cell cycle checkpoints, that ensure that initiation of a later event is coupled with the completion of an early cell cycle event. Deregulated proliferation is a characteristic feature of tumor cells. Moreover, defects in many of the molecules that regulate the cell cycle have been implicated in cancer formation and progression. Key among these are p53, the retinoblastoma protein (pRb) and its related proteins, p107 and pRb2/p130, and cdk inhibitors (p15, p16, p18, p19, p21, p27), all of which act to keep the cell cycle from progressing until all repairs to damaged DNA have been completed. The pRb (pRb/p16(INK4a)/cyclin D1) and p53 (p14(ARF)/mdm2/p53) pathways are the two main cell-cycle control pathways frequently targeted in tumorigenesis, and the alterations occurring in each pathway depend on the tumor type. Virtually all human tumors deregulate either the pRb or p53 pathway, and oftentimes both pathways simultaneously. This review focuses on the genetic and epigenetic alterations affecting the components of mechanisms regulating the progression of the cell cycle and leading to cancer formation and progression.
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
authors.forename: Marcella
authors.initials: M
authors.lastname: Macaluso
authors.forename: Micaela
authors.initials: M
authors.lastname: Montanari
authors.forename: Caterina
authors.initials: C
authors.lastname: Cinti
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53