title: Cell cycle control at the first restriction point and its effect on tissue growth.
abstract: Cell cycle is controlled at two restriction points, R (1) and R (2). At both points the cell will commit apoptosis if it detects irreparable damage. But at R (1) an undamaged cell also decides whether to proceed to the S phase or go into a quiescent mode, depending on the environmental conditions (e.g., overpopulation, hypoxia). We consider the effect of this decision at the population level in a spherical tissue {r < R(t)}. We prove that if the cells have full control at R (1), they can manipulate the size of R(t) to ensure that 0 < c <or= R(t) <or= C < infinity; simulations further show that R(t) can be made nearly stationary. In the absence of such control, R(t) will either increase to infinity or decrease to 0. The mathematical model and analysis involve a system of PDEs in {r < R(t)}.
authors.affiliation: Department of Mathematics, Mathematical Biosciences Institute, The Ohio State University, 231 West 18th Avenue, Columbus, OH 43210, USA. afriedman@math.ohio-state.edu
authors.forename: Avner
authors.initials: A
authors.lastname: Friedman
authors.forename: Bei
authors.initials: B
authors.lastname: Hu
authors.forename: Chiu-Yen
authors.initials: CY
authors.lastname: Kao
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological
references.citation: Cell. 1990 Jun 1;61(5):759-67
references.pmid: 2188735
references.citation: Science. 2004 Feb 6;303(5659):793-9
references.pmid: 14764867
references.citation: Theor Biol Med Model. 2006 Feb 10;3:7
references.pmid: 16472396
references.citation: Bull Math Biol. 2001 Mar;63(2):231-57
references.pmid: 11276525
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):27-30
references.pmid: 10592173
references.citation: Radiother Oncol. 1991 Nov;22(3):156-8
references.pmid: 1771254
references.citation: Biophys J. 2005 Dec;89(6):3884-94
references.pmid: 16199495
references.citation: J Math Biol. 2004 Aug;49(2):111-87
references.pmid: 15293017
references.citation: J Cell Sci. 1988 Aug;90 ( Pt 4):601-12
references.pmid: 3253297
references.citation: Trends Genet. 1997 Sep;13(9):375-6
references.pmid: 9287494
references.citation: Nat Rev Cancer. 2002 May;2(5):331-41
references.pmid: 12044009
references.citation: J Theor Biol. 2006 Dec 21;243(4):532-41
references.pmid: 16930628
references.citation: Bull Math Biol. 2001 Sep;63(5):801-63
references.pmid: 11565406