Loss of E2F-1 reduces tumorigenesis and extends the lifespan of Rb1(+/-)mice

Nature Genetics
L YamasakiT Jacks

Abstract

Mutation of the retinoblastoma tumour-suppressor gene (RB) leads to the deregulation of many proteins and transcription factors that interact with the retinoblastoma gene product (pRB), including members of the E2F transcription factor family. As pRB is known to repress E2F transcriptional activity and overexpression of E2F is sufficient for cell cycle progression, it is thought that pRB suppresses growth in part by repressing E2F-mediated transcription. Previously, we reported that loss of E2f1 in mice results in tissue-specific tumour induction and tissue atrophy, demonstrating that E2F-1 normally controls growth both positively and negatively in a tissue-specific fashion. To determine whether E2F-1 deregulation--as a result of loss of pRB--promotes proliferation in vivo, we have tested whether loss of E2f1 interferes with the pituitary and thyroid tumorigenesis that occurs in Rb1(+/-) mice. We have found that loss of E2f1 reduces the frequency of pituitary and thyroid tumours, and greatly lengthens the lifespan of Rb1(+/-); E2f1(-/-) animals, demonstrating that E2F-1 is an important downstream target of pRB during tumorigenesis. Furthermore, loss of E2f1 reduces a previously reported strain-dependent difference in Rb1(+/-) l...Continue Reading

References

Sep 24, 1992·Nature·T JacksR A Weinberg
Sep 24, 1992·Nature·A R ClarkeH te Riele
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·D G JohnsonJ R Nevins
Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·G XuW Krek
Jan 1, 1994·Annual Review of Cell Biology·D J RileyW H Lee
Aug 1, 1994·Nature Genetics·B O WilliamsT Jacks
Dec 1, 1994·Molecular and Cellular Biology·B Shan, W H Lee
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·X Q QinP D Adams
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·X Wu, A J Levine
May 17, 1996·Cell·L YamasakiN J Dyson
Dec 6, 1996·Science·C J Sherr
Jul 15, 1997·Genes & Development·A C PhillipsK H Vousden

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Citations

May 26, 1999·The Journal of Pathology·K F Macleod, T Jacks
Oct 12, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·W G Kaelin
Jul 13, 2002·Journal of Cellular Physiology·Tiziana ToniniPier Paolo Claudio
Mar 29, 2012·Amino Acids·Frank Gaunitz, Alan R Hipkiss
Dec 20, 2011·Protein & Cell·Gabriel M Gordon, Wei Du
Oct 10, 2001·Biochimica Et Biophysica Acta·M ZörnigG Evan
May 22, 2002·Biochimica Et Biophysica Acta·Michaela Herzig, Gerhard Christofori
May 22, 2002·Biochimica Et Biophysica Acta·James DeGregori
Feb 19, 2000·Current Opinion in Genetics & Development·K Macleod
Aug 21, 2001·Molecular Cell·G LeoneJ R Nevins
May 3, 2003·Cancer Cell·Hugh Cam, Brian David Dynlacht
Jul 2, 2003·Nature Cell Biology·Nicholas B La Thangue
Jul 2, 2003·Nature Cell Biology·Norbert M WikonkalDouglas E Brash
Apr 30, 2003·Nature Cell Biology·Craig StevensNicholas B La Thangue
Dec 24, 2005·Nature Reviews. Cancer·Benjamin D Rowland, Daniel S Peeper
Jan 15, 2009·Nature Reviews. Cancer·Erik S Knudsen, Karen E Knudsen
Oct 24, 2009·Nature Reviews. Cancer·Hui-Zi ChenGustavo Leone
Sep 25, 2009·Nature Reviews. Cancer·Shirley Polager, Doron Ginsberg
Aug 29, 2006·Oncogene·W Du, J Pogoriler
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Huifang SunDavid W Goodrich
Jun 12, 2010·Journal of Biochemistry·Yuanyan WeiJianhai Jiang
Jun 4, 2004·Genes & Development·Aaron AslanianJacqueline A Lees
Feb 17, 2006·Genes & Development·Timothy C Hallstrom, Joseph R Nevins
Jan 11, 2007·Genes & Development·Pamela L WenzelGustavo Leone
Dec 3, 2004·Genes & Development·Jan-Hermen DannenbergHein te Riele
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·P J IaquintaJ A Lees
Feb 10, 2000·Annals of the New York Academy of Sciences·A Y NikitinW H Lee
Jan 11, 2007·Molecular and Cellular Biology·Tiziana ParisiJacqueline A Lees
Mar 23, 2002·Molecular and Cellular Biology·Jennifer E CloudJacqueline A Lees

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