Abstract
Mutations of tumor suppressor genes remove mechanisms that normally arrest proliferation of transformed cells, resulting in tumor formation. The p53 gene product functions as a tumor suppressor that induces p21/Waf-1, the 21-kDa product of the waf-1/cip-1/mda-6 gene. p21/Waf-1 is a pan-cyclin-dependent kinase inhibitor that arrests cell cycle progression under a variety of circumstances. We examined tissues from a dog with multiple primary pigmented proliferative lesions (benign, multicentric melanoma consisting of three distinct dermal lesions and a matrical cyst) for p21/Waf-1 and p53 expression by immunohistochemistry and immunoblotting. p21/Waf-1 and p-53 proteins were undetectable in the tumor cells and in the cyst but were present in adjacent normal tissues. Abundant cyclin-dependent kinase 4 (Cdk4), a protein related functionally to p21/Waf-1, also was present in the cyst. A somatic mutation of the waf-1 gene or of the p53 gene may have resulted in the loss of p21/Waf-1 expression in a common precursor of pigment-producing cells from the affected dog. Furthermore, this functional loss of p21/Waf-1 may play an important role in the genesis of canine benign melanoma.
References
Jan 1, 1991·Cold Spring Harbor Symposia on Quantitative Biology·S MittnachtR A Weinberg
Jan 4, 1996·The New England Journal of Medicine·D S Latchman
Jun 30, 1995·Annals of the New York Academy of Sciences·R A Weinberg
Apr 1, 1995·Molecular Biology of the Cell·J W HarperE Swindell
May 5, 1995·Cell·R A Weinberg
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·M NakanishiJ R Smith
Oct 1, 1994·Clinics in Dermatology·M H Goldschmidt
Mar 9, 1995·Nature·D O Morgan
Nov 18, 1994·Cell·C J Sherr
Nov 18, 1994·Cell·T Hunter, J Pines
Nov 19, 1993·Cell·J W HarperS J Elledge
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Dec 16, 1993·Nature·Y XiongD Beach
Dec 1, 1995·Current Opinion in Cell Biology·E Lees
Jun 20, 1996·Nature·T Jacks, R A Weinberg
Jun 20, 1996·Nature·T WaldmanB Vogelstein
Mar 7, 1997·Cell·R A Weinberg
Citations
Aug 15, 2000·Cancer Letters·M G RittJ F Modiano
Jun 9, 1999·DNA and Cell Biology·J F ModianoR Smith
Jun 6, 2013·ISRN Veterinary Science·Jane M Dobson
Dec 6, 2008·In Vitro Cellular & Developmental Biology. Animal·Sarah W Kamau ChapmanMichael O Hottiger
Dec 9, 2003·Journal of Veterinary Internal Medicine·Shola S Sulaimon, Barbara E Kitchell
Dec 17, 2014·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Kelsey PoormanMatthew Breen
Jul 27, 2001·Veterinary Pathology·A KoenigJ F Modiano
Nov 27, 2002·Veterinary Pathology·S H SmithP M McManus
Jul 20, 2002·Veterinary Pathology·A KoenigJ F Modiano
Aug 29, 2003·Cancer Gene Therapy·Stacie R BiancoJaime F Modiano
Feb 13, 2019·Cancers·Lisa KoodieJulia Davydova
Jun 18, 2019·Melanoma Research·Katie L AndersonJaime F Modiano
Sep 18, 2015·The Journal of Biological Chemistry·Milcah C ScottJaime F Modiano
Nov 20, 2016·Cancer Immunology Research·Kipp WeiskopfJaime F Modiano
Apr 24, 2014·Molecular Cancer Therapeutics·Josef SingerErika Jensen-Jarolim
Nov 26, 2021·Veterinary Sciences·Laura Hardwick