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EN
Spontaneous mammary tumors are the most prevalent type of neoplasms in women as well as in female dogs. Although ovarian hormones estrogen and progesterone are known to play a key role in mammary tumorigenesis, conflicting reports have been obtained from in vivo and in vitro studies concerning the role of especially progesterone in mammary tumorigenesis. Prolonged exposure to high concentrations of progesterone during the unusually long luteal phase of the estrous cycle is suspected to be the key event in canine mammary tumorigenesis. Accordingly, previous studies have shown the development of mammary hyperplasia in dogs upon prolonged progestin administration. In this study, a dog-specific cDNA microarray was used to identify oncogenic determinants in progestin-induced canine hyperplasia (CMH) and spontaneous mammary tumors (CMC) by comparing expression profiles to those obtained from mammary glands of healthy dogs. The CMH profile showed elevated expression of genes involved in cell proliferation such as PCNA, NPY, RAN and also alterations in expression of transcription factors and cell adhesion molecules. Whereas in CMC, major alterations to the expression of genes involved in cell motility, cytoskeletal organization and extra cellular matrix production was evident besides differential expression of cell proliferation inducing genes. The overall gene expression profile of CMH was related to cell proliferation where as that of CMC was associated with both cell proliferation as well as neoplastic transformation. In conclusion, our findings support a strong cell proliferation inducing potential of progestins in the canine mammary gland. Moreover, deregulated genes identified in CMC are potentially involved in their malignant and may serve as prospective therapeutic targets.
EN
The aim of the study was to identify the genes responsible for the high growth rate and anti-apoptotic potential in selected canine mammary cancer cells. cDNA canine microarrays were used to compare the transcriptome in simple carcinoma CMT-U27 and spindle-cell tumor CMT-U309 cell lines. In CMT-U27 cell line the growth rate (shorter cell cycle), anti-apoptotic potential (higher expression of Bcl-2) was higher and spontaneous and induced apoptosis was lower. Comparison of transcriptomes revealed 333 genes which expression differed similarly. We focused on genes involved in cell proliferation, adhesion and apoptosis, and selected 29 of them. The high growth rate and anti-apoptotic potential in CMT-U27 cells was associated with enhanced expression of genes (at the level of transcripts) involved in Ca2+ signaling pathway (Calmodulin 1, 2, 3 and SPSB2) and growth hormone cellular pathway. The low-proliferative and pro-apoptotic phenotype of CMT-U309 cells was more dependent on TGFß, neuregulin 1 pathways and adhesion-related molecules.
3
Content available remote Comparison of cellular and tissue transcriptional profiles in canine mammary tumor
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EN
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.
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