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Comparison of cellular and tissue transcriptional profiles in canine mammary tumor

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Tumor-derived cell lines are widely used as in vitro cancer models. Cell lines historically served as the primary experimental model systems for exploration of tumor cell biology and pharmacology. However, their ability to accurately reflect the phenotype and genotype of the parental histology remains questionable, given the prevalence of documented cell line-specific cytogenetic changes. Sometimes cell line studies are interpreted in the context of artifacts introduced by selection and establishment of cell lines in vitro. This complication has led to difficulties in the extrapolation of biology observed in cell lines to tumor biology in vivo. The aim of our study was to compare gene expression profiles in canine mammary tumor tissue and cell cultures derived from those tumors using cDNA microarrays. Tumors of two different origins were used; chondrosarcoma and adenocarcinoma and their primary cell cultures. It has been found that cell culture gene expression profiles closely resembled those of their corresponding in vivo tumor. In adenocarcinoma and chondrosarcoma only 6.0% and 2.7% of genes respectively, have shown significant difference in expression. In the most cases the difference concerned up-regulation of gene expression in cell lines, particularly genes involved in: protein metabolism and modification, signal transduction and nucleotide, nucleoside and nucleic acid metabolism. These experiments revealed that transcriptome of our primary cell culture corresponds to transcriptome of its parental tumor tissue and for this reason cell culture represents the reliable in vitro model for oncogenomic and pharmacogenomic studies.
The expression of p53 protein was determined by the immunohistochemical study with CM-1 polyclonal antibody. The investigations were performed on formalin-fixed and paraffin-embedded tissue samples of mammary tumours obtained from 131 bitches during surgery. The p53 protein accumulation was detected in 37 tumours (28.24%). No correlation was found between p53 protein overexpression and histological type, tumour size, or regional lymph node status. However, its relationship with a histologic malignant grade approached statistical significance (P=0.067). After the 24-month follow-up period, survival analysis revealed a shortened disease-free survival and overall survival time of the dogs with tumours, which overexpressed p53 protein. Only in the case of survival time, the difference was close to the borderline of statistical significance (P=0.061). The research data presented herein, being not fully explicit, have indicated a correlation of p53 protein accumulation with worse prognosis in canine mammary tumours, although the results do not allow recognising p53 protein accumulation as a suitable prognostic factor.
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