Invasive melanoma in Cdk4-targeted mice

Proceedings of the National Academy of Sciences of the United States of America
Rocio SotilloMarcos Malumbres

Abstract

Many human tumors harbor mutations that result in deregulation of Cdk4 activity. Most of these mutations involve overexpression of D-type cyclins and inactivation of INK4 inhibitors. In addition, a mutation in the Cdk4 protein has been described in patients with familial melanoma (Wolfel, T., Hauer, M., Schneider, J., Serrano, M., Wolfel, C., et al. (1995) Science 269, 1281-1284; Zuo, L., Weger, J., Yang, Q., Goldstein, A. M., Tucker, M. A., et al. (1996) Nat. Genet. 12, 97-99). This mutation, R24C, renders the Cdk4 protein insensitive to inhibition by INK4 proteins including p16(INK4a), a major candidate for the melanoma susceptibility locus. Here we show that knock-in mice expressing a Cdk4 R24C allele are highly susceptible to melanoma development after specific carcinogenic treatments. These tumors do not have mutations in the p19(ARF)/p53 pathway, suggesting a specific involvement of the p16(INK4a)/Cdk4/Rb pathway in melanoma development. Moreover, by using targeted mice deficient for other INK4 inhibitors, we show that deletion of p18(INK4c) but not of p15(INK4b) confers proliferative advantage to melanocytic tumor growth. These results provide an experimental scenario to study the role of Cdk4 regulation in melanoma and ...Continue Reading

References

Sep 18, 1998·Frontiers in Bioscience : a Journal and Virtual Library·F MeierM Herlyn
Nov 21, 1998·Biochimica Et Biophysica Acta·M Ruas, G Peters
Dec 1, 1998·Genes & Development·L ChinR A DePinho
Mar 11, 1999·Current Opinion in Genetics & Development·N E Sharpless, R A DePinho
Jun 23, 1999·Oncogene·C M Lee, E P Reddy
Sep 28, 1999·Oncogene·M F Roussel
Dec 14, 1999·Molecular and Cellular Biology·F ZindyM F Roussel
May 20, 2000·Advances in Cancer Research·N BardeesyL Chin
Nov 15, 2000·Biological Chemistry·M MalumbresM Barbacid
Mar 10, 2001·Molecular and Cellular Biology·N BardeesyL Chin

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Citations

Jun 30, 2005·Cancer Metastasis Reviews·Ruth Halaban
Nov 28, 2012·Cancer Metastasis Reviews·Michael D GoberJohn T Seykora
May 7, 2009·Transgenic Research·Weimin LiPhilipp Kaldis
Jul 28, 2006·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M Pons, M Quintanilla
Jan 26, 2002·Lancet·Graeme J Walker, Nicholas K Hayward
Mar 20, 2002·Biochimie·Brigitte Bressac-de-PailleretsFlorence Demenais
Apr 19, 2002·Biochimica Et Biophysica Acta·Sagrario OrtegaMariano Barbacid
Mar 27, 2003·Trends in Molecular Medicine·Glenn Merlino, Frances P Noonan
Aug 10, 2007·Nature Reviews. Cancer·Kristopher K Frese, David A Tuveson
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Dec 3, 2003·Oncogene·Paula L Miliani de MarvalMarcelo L Rodriguez-Puebla
Jan 10, 2003·The Journal of Investigative Dermatology. Symposium Proceedings·Andrzej DlugoszStuart H Yuspa
Jul 11, 2006·The New England Journal of Medicine·Arlo J Miller, Martin C Mihm
Jun 27, 2002·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Richard Marcotte, Eugenia Wang
Sep 22, 2012·Journal of the National Cancer Institute·Ahmad JaliliStephan N Wagner
Nov 3, 2004·Genes & Development·Ander MatheuManuel Serrano
Jul 24, 2010·Pigment Cell & Melanoma Research·Jennifer LandsbergThomas Tüting
Aug 20, 2010·Pigment Cell & Melanoma Research·Blake FergusonGraeme J Walker
Sep 21, 2010·Pigment Cell & Melanoma Research·Tamara TerzianNeil F Box
Oct 27, 2010·Pigment Cell & Melanoma Research·William E Damsky, Marcus Bosenberg
Oct 12, 2011·Pigment Cell & Melanoma Research·Graeme J WalkerNeil F Box
Feb 2, 2006·Molecular and Cellular Biology·James DeGregori
Apr 30, 2009·Annual Review of Pathology·Nageatte Ibrahim, Frank G Haluska
Jul 18, 2008·Cancer Research·Keiran S M SmalleyKatherine L Nathanson
Mar 19, 2004·Neurosurgery·Stacey M Ivanchuk, James T Rutka
Apr 15, 2006·Expert Review of Anticancer Therapy·Harriet Wikman, Eeva Kettunen
Aug 26, 2010·Pharmaceuticals·Janet Wangari-TalbotSuzie Chen
Aug 22, 2015·Cell Death and Differentiation·V QueredaM Malumbres
Apr 5, 2011·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·André A FernandezDavid L Mitchell
Oct 31, 2002·The Journal of Investigative Dermatology·Graeme J Walker, Nicholas K Hayward
Jul 16, 2015·The Journal of Investigative Dermatology·Allen W Ho, Hensin Tsao
Sep 13, 2008·The Journal of Investigative Dermatology·M Raza ZaidiGlenn Merlino
Dec 28, 2007·Advances in Dermatology·Whitney A High, William A Robinson
Jan 9, 2007·Current Opinion in Genetics & Development·Marcos Malumbres, Mariano Barbacid
Oct 10, 2008·Aging Cell·Sebastian HaferkampHelen Rizos
Oct 16, 2007·Pigment Cell Research·Lionel Larue, Friedrich Beermann
Jan 6, 2011·International Journal of Cancer. Journal International Du Cancer·Evelyn GaffalThomas Tüting
Jan 26, 2010·Actas dermo-sifiliográficas·S BloethnerR Kumar
Oct 21, 2005·Trends in Biochemical Sciences·Marcos Malumbres, Mariano Barbacid
Apr 12, 2005·European Journal of Cell Biology·Sibylle Mittnacht
Aug 7, 2002·The American Journal of Pathology·Marcelo L Rodriguez-PueblaClaudio J Conti

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