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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.
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.
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Age-dependent changes in bovine skeletal muscle transcriptomic profile

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The postnatal growth of muscle tissue occurs by hypertrophy comprising satellite cells proliferation, differentiation and protein turnover. The highest rate of skeletal muscle gains and protein synthesis in bulls occurs in the period between 180 and 360 days of postnatal life. However, genes which are responsible for quantitative and qualitative changes in skeletal muscle during this period are not identified up to date. The aim of our study was to compare the changes in transcriptomic profile of skeletal muscle (m. semitendinosus) in 12 Polish Black and White bulls between 6 and 12 month of life. For experimental purposes we used bovine cDNA microarray (the NBFGC EST collection) which contains 18,263 unique genes, derived from many different tissue types and various physiologically important states within these tissues. Our results revealed 53 genes which expression changed in the same manner depending on age of all examined pairs of animals. Thirty two of these genes showed at least 2-fold difference in expression between two analyzed age points. Age-dependent up-regulation was the most pronounced in the case of following genes: similar to MAD2L1 binding protein, similar to thymocyte potein thy28 isoform 1, similar to type I inositol-1,4,5-triphosphate 5-phosphatase, similar to nucleoside diphosphate kinase 6, proline rich 14, similar to transcription factor E2-alpha and phospholipase C gamma 1. The highest age-dependent decrease of the transcript was observed in the case of: similar to ubiquitin carboxy-terminal hydrolase L1, similar to latent TGF-beta binding protein 3 precursor, phospho-mannomutase 2, CD74 antigen, simlar to BCL6 co-represor-like 1, plateled/endothelial cell adhesion molecule (PECAM1), necdin, zygin, tight junction protein 3, ankyrin and apolipoprotein-L3. Although the role of the most of above genes and interactions between products of their expression is not clear at the moment, the significance of their response between 6 and 12 month of age may indicate their involvement in growth, development and metabolic changes in bovine skeletal muscle during the first year of postnatal life.
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