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

Michelle G Ritt, J. Wojcieszyn, Jaime Modiano

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)94-101
Number of pages8
JournalVeterinary Pathology
Volume35
Issue number2
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

melanoma
Canidae
Cysts
Melanoma
p53 Genes
cyclin-dependent kinase
dogs
lesions (animal)
Cyclin-Dependent Kinase 4
Dogs
Neoplasms
Mutation
genes
Cyclin-Dependent Kinases
Cell Cycle Checkpoints
Tumor Suppressor Genes
Immunoblotting
somatic mutation
Genes
neoplasms

Keywords

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

Cite this

Functional loss of p21/Waf-1 in a case of benign canine multicentric melanoma. / Ritt, Michelle G; Wojcieszyn, J.; Modiano, Jaime.

In: Veterinary Pathology, Vol. 35, No. 2, 01.01.1998, p. 94-101.

Research output: Contribution to journalArticle

Ritt, Michelle G ; Wojcieszyn, J. ; Modiano, Jaime. / Functional loss of p21/Waf-1 in a case of benign canine multicentric melanoma. In: Veterinary Pathology. 1998 ; Vol. 35, No. 2. pp. 94-101.
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