Centrosome Amplification and Chromosomal Instability in Feline Lymphoma Cell Lines

Abstract

ABSTRACT. To evaluate the presence of centrosome amplification and the resulting chromosomal instability in cat tumors, a newly established feline lymphoma cell line and four already established feline lymphoma cell lines were examined using immunohistochemical analysis of centrosomes. The number of chromosomes were subsequently counted by metaphase spread. Moreover, to explore whether mutational inactivation of the p53 gene or inactivation of the P53 protein caused by mdm2 gene overexpression, occurred in the feline lymphoma cell lines, mutational analysis of the feline p53 gene was carried out. The expression of feline mdm2 mRNA was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Centrosome amplification and chromosomal instability was observed in three out of the five feline lymphoma cell lines. Of these three feline lymphoma cell lines, one had aberrations in the P53 amino-acid sequence, whereas the others had none. There was no significant difference in the expression of mdm2 mRNA between peripheral blood mononuclear cells (PBMC) obtained from a normal cat and that of the five feline lymphoma cell lines. These findings indicate th at centrosome amplification also occurs in cat tumors and is strongly correlated with chromosomal instability, suggesting that the immunostaining of centrosomes could be an alternative method for the examination of the chromosomal instability. Furthermore, this study s uggests the presence of unknown mechanism that leads to the centrosome amplification in feline lymphomas.

The transmembrane domain is essential for the microtubular trafficking of membrane type-1 matrix metalloproteinase (MT1-MMP)

“…Centrosomes are characterized by ␥-tubulincontaining centrioles surrounded by pericentriolar material. Alterations in the centrosome functionality lead to the formation of abnormal mitotic spindles and to premature anaphase and chromosome instability, the latter being routine and frequent features of highly aggressive tumors (Miki et al, 2004;Nakajima et al, 2004;Wang et al, 2004b).…”

Exclusion of RUNX3 as a tumour-suppressor gene in early-onset gastric carcinomas

“…Nuclear spreads of the 14 cell lines were prepared as described previously (Miki et al, 2004). The nuclear spreads were airdried and baked overnight at 601C.…”

Cloning of the Feline GADD45 cDNA and Analysis of its Mutation in Feline Lymphoma Cell Lines

“…Recently, Miki et al reported that chromosome instability and consequent centrosome amplification were observed in feline lymphoma cell lines, although they showed a wildtype p53 status [19]. Based on this information, we examined whether GADD45 mutations under certain conditions could substitute for the p53 mutations in feline oncogenesis.…”

“…Functional inactivation of P53 is a very common event in many types of human cancers [8] and is a key step in oncogenesis [9]. Moreover, p53 mutations have been shown not only in human tumors, but also in feline tumors [19,22].…”