![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RESEARCH PAPER
1 Department of Biology and 2 Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; 3 Howard Hughes Medical Institute, Chevy Chase, Maryland 20185, USA
Certain cells of the human retina are extremely sensitive to loss of function of the retinoblastoma tumor suppressor gene RB. Retinoblastomas develop early in life and at high frequency in individuals heterozygous for a germ-line RB mutation, and sporadic retinoblastomas invariably have somatic mutation in the RB gene. In contrast, retinoblastomas do not develop in Rb+/- mice. Although retinoblastoma is thought to have developmental origins, the function of Rb in retinal development has not been fully characterized. Here we studied the role of Rb in normal retinal development and in retinoblastoma using conditional Rb mutations in the mouse. In late embryogenesis, Rb-deficient retinas exhibited ectopic S-phase and high levels of p53-independent apoptosis, particularly in the differentiating retinal ganglion cell layer. During postnatal retinal development, loss of Rb led to more widespread retinal apoptosis, and adults showed loss of photoreceptors and bipolar cells. Conditional Rb mutation in the retina did not result in retinoblastoma formation even in a p53-mutant background. However, on a p107- or p130-deficient background, Rb mutation in the retina caused retinal dysplasia or retinoblastoma.
[Keywords: Retinoblastoma; p130; p107; p53; apoptosis]
Received March 16, 2004; revised version accepted May 18, 2004.
Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1203304.
4 Present address: Department of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
5 Corresponding author.
E-MAIL tjacks{at}mit.edu; FAX (617) 253-9863.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. A.P. Martins, F. Zindy, S. Donovan, J. Zhang, S. Pounds, A. Wey, P. S. Knoepfler, R. N. Eisenman, M. F. Roussel, and M. A. Dyer N-myc coordinates retinal growth with eye size during mouse development Genes & Dev., January 15, 2008; 22(2): 179 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Weber, M. K. Corbett, L. M. L. Chow, M. B. Valentine, S. J. Baker, and J. Zuo Rapid cell-cycle reentry and cell death after acute inactivation of the retinoblastoma gene product in postnatal cochlear hair cells PNAS, January 15, 2008; 105(2): 781 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. MacPherson and M. A. Dyer Retinoblastoma: From the Two-Hit Hypothesis to Targeted Chemotherapy Cancer Res., August 15, 2007; 67(16): 7547 - 7550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. McClellan, V. A. Ruzhynsky, D. N. Douda, J. L. Vanderluit, K. L. Ferguson, D. Chen, R. Bremner, D. S. Park, G. Leone, and R. S. Slack Unique Requirement for Rb/E2F3 in Neuronal Migration: Evidence for Cell Cycle-Independent Functions Mol. Cell. Biol., July 1, 2007; 27(13): 4825 - 4843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Johnson, J. Zhang, S. Frase, M. Wilson, C. Rodriguez-Galindo, and M. A. Dyer Neuronal Differentiation and Synaptogenesis in Retinoblastoma Cancer Res., March 15, 2007; 67(6): 2701 - 2711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Parisi, T. L. Yuan, A. M. Faust, A. M. Caron, R. Bronson, and J. A. Lees Selective Requirements for E2f3 in the Development and Tumorigenicity of Rb-Deficient Chimeric Tissues Mol. Cell. Biol., March 15, 2007; 27(6): 2283 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Lee, D. Almeida, N. Claros, D. H. Abramson, and D. Cobrinik Cell Cycle-Specific and Cell Type-Specific Expression of Rb in the Developing Human Retina Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5590 - 5598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.-S. Moon, L. Di Stefano, and N. Dyson A Gradient of Epidermal Growth Factor Receptor Signaling Determines the Sensitivity of rbf1 Mutant Cells to E2F-Dependent Apoptosis Mol. Cell. Biol., October 15, 2006; 26(20): 7601 - 7615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Elison, D. Cobrinik, N. Claros, D. H. Abramson, and T. C. Lee Small Molecule Inhibition of HDM2 Leads to p53-Mediated Cell Death in Retinoblastoma Cells. Arch Ophthalmol, September 1, 2006; 124(9): 1269 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhou, A. Flesken-Nikitin, D. C. Corney, W. Wang, D. W. Goodrich, P. Roy-Burman, and A. Yu. Nikitin Synergy of p53 and Rb Deficiency in a Conditional Mouse Model for Metastatic Prostate Cancer Cancer Res., August 15, 2006; 66(16): 7889 - 7898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sun, Y. Chang, B. Schweers, M. A. Dyer, X. Zhang, S. W. Hayward, and D. W. Goodrich An E2F Binding-Deficient Rb1 Protein Partially Rescues Developmental Defects Associated with Rb1 Nullizygosity Mol. Cell. Biol., February 15, 2006; 26(4): 1527 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Haigis, J. Sage, J. Glickman, S. Shafer, and T. Jacks The Related Retinoblastoma (pRb) and p130 Proteins Cooperate to Regulate Homeostasis in the Intestinal Epithelium J. Biol. Chem., January 6, 2006; 281(1): 638 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Laurie, J. K. Gray, J. Zhang, M. Leggas, M. Relling, M. Egorin, C. Stewart, and M. A. Dyer Topotecan Combination Chemotherapy in Two New Rodent Models of Retinoblastoma Clin. Cancer Res., October 15, 2005; 11(20): 7569 - 7578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. N. Mayhew, E. E. Bosco, S. R. Fox, T. Okaya, P. Tarapore, S. J. Schwemberger, G. F. Babcock, A. B. Lentsch, K. Fukasawa, and E. S. Knudsen Liver-Specific pRB Loss Results in Ectopic Cell Cycle Entry and Aberrant Ploidy Cancer Res., June 1, 2005; 65(11): 4568 - 4577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mantela, Z. Jiang, J. Ylikoski, B. Fritzsch, E. Zacksenhaus, and U. Pirvola The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear Development, May 15, 2005; 132(10): 2377 - 2388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Dannenberg, L. Schuijff, M. Dekker, M. van der Valk, and H. t. Riele Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107 and p130 Genes & Dev., December 1, 2004; 18(23): 2952 - 2962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Marchong, D. Chen, T. W. Corson, C. Lee, M. Harmandayan, E. Bowles, N. Chen, and B. L. Gallie Minimal 16q Genomic Loss Implicates Cadherin-11 in Retinoblastoma Mol. Cancer Res., September 1, 2004; 2(9): 495 - 503. [Abstract] [Full Text] [PDF]
|
|
