Tumor suppressor PTEN is mutated in canine osteosarcoma cell lines and tumors.
Canine osteosarcoma (OS) cell lines contain mutations that directly or indirectly inactivate the tumor suppressor genes p53 and retinoblastoma. Another important tumor suppressor, PTEN, is mutated in many human cancers. To determine whether inactivation of PTEN plays a role in the pathogenesis of canine OS, we studied its expression in canine OS cell lines and tumors. Four of five canine OS cell lines (CO2, C03, CO5, and CO7) constitutively express high levels of the phosphorylated form of Akt, an indirect indicator of aberrant PTEN expression. PTEN protein is essentially absent from three of these cell lines (CO2, CO5, and CO7), whereas C03 contains a potentially inactivating amino acid substitution in PTEN at codon 340. Genomic hybridization experiments indicate that CO2, CO5, and CO7 contain large deletions within the PTEN gene. Ten of 15 OS tumors exhibit variable or negative PTEN staining. Evaluation of a PTEN-negative staining tumor by Southern blotting indicates that the PTEN gene is deleted in this tumor. These results indicate that PTEN is mutated or downregulated in a high percentage of canine OS cell lines and tumors and likely plays an important role in the pathogenesis of the disease.
Levine
R A
RA
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. ral1@cornell.edu
Forest
T
T
Smith
C
C
D000818:Animals; D015152:Blotting, Northern / Q000662:veterinary; D015139:Blotting, Southern / Q000662:veterinary; D015153:Blotting, Western / Q000662:veterinary; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry / Q000662:veterinary; D008297:Male; D009154:Mutation; D009693:Nucleic Acid Hybridization; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase