Requirement for both Shc and phosphatidylinositol 3' kinase signaling pathways in polyomavirus middle T-mediated mammary tumorigenesis.

Molecular and Cellular Biology
M A WebsterWilliam J Muller

Abstract

Transgenic mice expressing the polyomavirus (PyV) middle T antigen (MT) develop multifocal mammary tumors which frequently metastasize to the lung. The potent transforming activity of PyV MT is correlated with its capacity to activate and associate with a number of signaling molecules, including the Src family tyrosine kinases, the 85-kDa Src homology 2 subunit of the phosphatidylinositol 3' (PI-3') kinase, and the Shc adapter protein. To uncover the role of these signaling proteins in MT-mediated mammary tumorigenesis, we have generated transgenic mice that express mutant PyV MT antigens decoupled from either the Shc or the PI-3' kinase signaling pathway. In contrast to the rapid induction of metastatic mammary tumors observed in the strains expressing wild-type PyV MT, mammary epithelial cell-specific expression of either mutant PyV MT resulted in the induction of extensive mammary epithelial hyperplasias. The mammary epithelial hyperplasias expressing the mutant PyV MT defective in recruiting the PI-3' kinase were highly apoptotic, suggesting that recruitment of PI-3' kinase by MT affects cell survival. Whereas the initial phenotypes observed in both strains were global mammary epithelial hyperplasias, focal mammary tumors e...Continue Reading

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·C T GuyW J Muller
Nov 1, 1992·The Journal of Cell Biology·Y GavrieliS A Ben-Sasson
Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·G WalterM Mumby
Nov 25, 1987·Biochimica Et Biophysica Acta·W Markland, A E Smith
Jun 1, 1994·Molecular and Cellular Biology·S P SoltoffL C Cantley
Feb 16, 1995·Nature·T Pawson
Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·M A WebsterW J Muller
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·C L AddisonF L Graham
May 26, 1995·The Journal of Biological Chemistry·W SuT M Roberts
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·K S CampbellD C Pallas
Mar 15, 1997·Genes & Development·S G KennedyN Hay
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·R BronsonT Benjamin

❮ Previous
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Citations

Jan 9, 2001·The Journal of Investigative Dermatology. Symposium Proceedings·R Klafter, J L Arbiser
Jun 10, 2009·Seminars in Cancer Biology·Jingwei ChengBrian S Schaffhausen
Jan 10, 2006·The American Journal of Pathology·Grace CecenaRobert G Oshima
Aug 18, 2012·Stem Cells·Natesh ParashuramaSanjiv S Gambhir
Oct 15, 2013·British Journal of Pharmacology·Concetta Bubici, Salvatore Papa
Sep 6, 2002·The American Journal of Pathology·Andrea RosnerRobert D Cardiff
Sep 6, 2002·Biochemical Pharmacology·James HulitRichard G Pestell
Nov 26, 2009·Cell·Kandice R LeventalValerie M Weaver
Nov 5, 1999·Annual Review of Microbiology·A RoulstonP E Branton
May 13, 2005·Mutation Research·Qiang Shen, Powel H Brown
Nov 5, 2016·The Journal of Experimental Medicine·Sylvain DelaunayPierre Close
Mar 8, 2007·Carcinogenesis·Carmen Blanco-AparicioAmancio Carnero
Jun 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Peter M SiegelJoan Massagué
Nov 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Zhijun DuYi Li
Apr 26, 2007·Proceedings of the National Academy of Sciences of the United States of America·Alana L WelmJ Michael Bishop
Jun 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Richard MarcotteWilliam J Muller
Jul 19, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Carlos L Arteaga
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M AokiP K Vogt
Aug 24, 1999·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·M L OliveiraM C Sogayar
Oct 23, 2008·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Oliver RennerAmancio Carnero
Sep 8, 2017·International Journal of Molecular Sciences·Julio Cesar M de-Freitas-JuniorSalomé S Pinho
Dec 9, 2003·Oncogene·Katerina PolitiArgiris Efstratiadis
Apr 6, 2018·Cancer & Metabolism·Chen DaiLaurie E Littlepage
Mar 2, 2011·The Journal of Biological Chemistry·Shreya MitraCarla Lynn Van den Berg
Feb 15, 2008·The EMBO Journal·Josie Ursini-SiegelWilliam J Muller
Jul 25, 2008·Journal of Mammary Gland Biology and Neoplasia·Richard Marcotte, William J Muller
May 18, 2005·Oncogene·Azzah Al Masri, Sandra J Gendler
Jul 12, 2005·Oncogene·John A TynanRobert G Oshima
Sep 1, 2005·Clinical & Experimental Metastasis·Alexander D BorowskyJeffrey P Gregg
Sep 14, 2012·The Biochemical Journal·Melanie K B Wills, Nina Jones

❮ Previous
Next ❯

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