Functional loss of p21/Waf-1 in a case of benign canine multicentric melanoma.
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.
Ritt
M G
MG
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station 77843-4467, USA.
Wojcieszyn
J
J
Modiano
J F
JF
D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000737:chemistry / Q000502:physiology*; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005552:Forelimb / Q000473:pathology; D005887:Gingival Neoplasms / Q000473:pathology / Q000662:veterinary; D015151:Immunoblotting / Q000662:veterinary; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000662:veterinary*; D009669:Nose Neoplasms / Q000473:pathology / Q000662:veterinary; D015689:Oncogene Protein p21(ras) / Q000737:chemistry / Q000502:physiology*; D010784:Photomicrography / Q000662:veterinary; D016160:Retinoblastoma Protein / Q000737:chemistry; D012878:Skin Neoplasms / Q000473:pathology / Q000662:veterinary; D013623:Tail / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D015689:Oncogene Protein p21(ras)