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

M. G. Ritt, J. Wojcieszyn, J. F. Modiano

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)94-101
Number of pages8
JournalVeterinary pathology
Issue number2
StatePublished - Mar 1998


  • Canine
  • Cyclin-dependent kinase inhibitors
  • Immunoblotting
  • Immunohistochemistry
  • Melanoma
  • Tumor suppressor genes


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