PMID: 9539362Apr 16, 1998Paper

Functional loss of p21/Waf-1 in a case of benign canine multicentric melanoma

Veterinary Pathology
M G RittJ F Modiano

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.

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Citations

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
Nov 27, 2002·Veterinary Pathology·S H SmithP M McManus
Aug 29, 2003·Cancer Gene Therapy·Stacie R BiancoJaime F Modiano
Sep 18, 2015·The Journal of Biological Chemistry·Milcah C ScottJaime F Modiano
Apr 24, 2014·Molecular Cancer Therapeutics·Josef SingerErika Jensen-Jarolim

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