Effect of an adenoviral vector that expresses the canine p53 gene on cell growth of canine osteosarcoma and mammary adenocarcinoma cell lines

Abstract

AxCA-cp53 inhibits cell growth via induction of cell cycle arrest and apoptosis in canine osteosarcoma and mammary adenocarcinoma cell lines that lack a functional p53 gene. AxCA-cp53 may be useful to target the p53 gene in the treatment of dogs with tumors.

Anti-Tumor Effect of Adenoviral Vector-Mediated p53 Gene Transfer on the Growth of Canine Osteosarcoma Xenografts in Nude Mice

“…Both of the POS and CHOS cell lines were shown to have missense point mutations at codons 162 (CGC to CAC, Arg to His) (unpublished data) and 150 (TAT to AAT, Try to Asn) [36], respectively. Immunohistochemical analyses revealed overexpression of P53, possibly derived from their mutated p53 genes in both POS and CHOS cells [36].…”

“…Both of the POS and CHOS cell lines were shown to have missense point mutations at codons 162 (CGC to CAC, Arg to His) (unpublished data) and 150 (TAT to AAT, Try to Asn) [36], respectively. Immunohistochemical analyses revealed overexpression of P53, possibly derived from their mutated p53 genes in both POS and CHOS cells [36]. These two cell lines were cultured in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum, penicillin (100 U/ml), and streptomycin (100 g/ml) at 37°C in a humidified atmosphere of 5% CO 2 .…”

“…Construction and generation of the adenoviral vectors: An adenoviral vector that expresses wild-type canine P53 (AxCA-cp53) was generated by use of a commercial adenoviral vector kit (Adenovirus expression vector kit, Takara, Kyoto, Japan) as previously reported [36]. Briefly, a canine p53 cDNA fragment was inserted into an expression cassette cosmid vector, pAxCAwt, between the CAG promoter (ie, cytomegalovirus enhancer and chicken β-actin promoter) and rabbit β-globin polyadenylation signal site.…”

“…For the treatment of canine osteosarcoma, we constructed an adenovirus vector inserted with canine p53 gene. We previously reported that a recombinant replication-defective adenoviral vector expressing canine wild-type P53 (AxCA-cp53) inhibited cell growth via induction of cell cycle arrest and apoptosis in canine osteosarcoma and mammary adenocarcinoma cell lines [36]. As an extension of that study, the present study was carried out to evaluate the anti-tumor effect of intratumoral injection with AxCA-cp53 in canine osteosarcoma xenografts formed in nude mice.…”

Mutation of p53 Gene and Its Correlation with the Clinical Outcome in Dogs with Lymphoma

“…A canine mammary gland tumor cell line (cIPm) was used as a control to have wild‐type p53 gene. Cell lines with known p53 mutation; a canine osteosarcoma cell line (cHOS) and a canine mammary gland carcinoma cell line (cHMp) were used to verify the conditions of SSCP.…”