Homo sapiens
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PROVIDER: PRJNA105685 | ENA |
REPOSITORIES: ENA
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Project description:Metaphase comparative genomic hybridisation (CGH) studies indicate that chromosomes 4, 5, 6, 13, 14, 15 and 18 are frequently deleted in primary ovarian cancers (OC). Therefore, we used microcell-mediated chromosome transfer (MMCT) to establish the functional effects of transferring normal copies of these chromosomes into two epithelial OC cell lines. The in vitro neoplastic phenotype (measured as anchorage dependent and independent growth and invasion) was compared between recipient OC cell lines and multiple MMCT hybrids. Chromosomes 6 and 18 showed strong evidence of functional, neoplastic suppression for multiple hybrids in both cell lines. We also found evidence in one cancer cell line suggesting that chromosomes 4, 13 and 14 may also cause functional suppression. Array CGH and microsatellite analyses were used to characterise the extent of genomic transfer in chromosome 6 and 18 hybrids. A 35Mb deletion on chromosome 6 in two hybrids from one cell line mapped the candidate region proximal to 6q15 and distal to 6q22.2; and an approximate 10Mb candidate region spanning the centromere on chromosome 18 was identified in another two hybrids from the other cell line. These data confirm reported functional effects of chromosome 6 in OC cell lines; but to our knowledge, this is the first time that functional suppression for chromosome18 has been reported. This suggests that these chromosomes may harbour genes that behave as tumour suppressors. The future identification of these genes may have a significant impact on the understanding and treatment of the disease and the identification of novel therapeutic targets. Four clones from chr 6 and chr 18 hybrids that were transferred by MMCT successfully were mapped by CGH microarray to identified transferred regions that induced neoplastic suppression in epithelial ovarian cancer cell lines (TOV21G and TOV112D).
2008-08-19 | E-GEOD-11872 | biostudies-arrayexpress
Project description:Metaphase comparative genomic hybridisation (CGH) studies indicate that chromosomes 4, 5, 6, 13, 14, 15 and 18 are frequently deleted in primary ovarian cancers (OC). Therefore, we used microcell-mediated chromosome transfer (MMCT) to establish the functional effects of transferring normal copies of these chromosomes into two epithelial OC cell lines. The in vitro neoplastic phenotype (measured as anchorage dependent and independent growth and invasion) was compared between recipient OC cell lines and multiple MMCT hybrids. Chromosomes 6 and 18 showed strong evidence of functional, neoplastic suppression for multiple hybrids in both cell lines. We also found evidence in one cancer cell line suggesting that chromosomes 4, 13 and 14 may also cause functional suppression. Array CGH and microsatellite analyses were used to characterise the extent of genomic transfer in chromosome 6 and 18 hybrids. A 35Mb deletion on chromosome 6 in two hybrids from one cell line mapped the candidate region proximal to 6q15 and distal to 6q22.2; and an approximate 10Mb candidate region spanning the centromere on chromosome 18 was identified in another two hybrids from the other cell line. These data confirm reported functional effects of chromosome 6 in OC cell lines; but to our knowledge, this is the first time that functional suppression for chromosome18 has been reported. This suggests that these chromosomes may harbour genes that behave as tumour suppressors. The future identification of these genes may have a significant impact on the understanding and treatment of the disease and the identification of novel therapeutic targets.
2008-08-19 | GSE11872 | GEO
Project description:Ovarian cancer is one of the most deadly cancers accounting for only 3% of diagnosed cancers, but is the fifth leading cause of cancer deaths among woman; however, the progression of ovarian cancer is poorly understood. To study and further understand the early events that lead to epithelial derived ovarian cancer, we previously developed a cell model of progressive ovarian cancer. Mouse ovarian surface epithelial (MOSE) cells have undergone spontaneous transformation in cell culture and represent pre-neoplastic, non-tumorigenic to an aggressive malignant phenotype. Microarray analysis was performed with RNA isolated from different stages of MOSE cells to examine changes in gene expression as MOSE cells transition from a pre-neoplastic to a malignant state. RNA was isolated from MOSE early cell representing a pre-neoplastic, non-malignant stage, MOSE Intermediate cells representing a noeplastic, pre-invasive state, and MOSE Late cells representing a malignant, invasive stage. Three biological replicates were used to take into account variations within the heterogeneous cultures.
2011-03-03 | E-GEOD-24789 | biostudies-arrayexpress
Project description:The human kinome is incolved in multiple function in the life cycle of cells, and ther differntial expression in cacner suggests that protein kinases play an important role in tumor progression and proliferation. To delineate pathways that may be important for neoplastic change in women at high risk for ovarian cancer, we compared the expression signature of surface kinases in normal ovarian surface epithelium with ovarian epithelium from patients at high risk, and epithelial ovarian cancer using Affymetrix expresion array HG U133Plus2. A total of 18 ovarian samples were collected. The number of samples and subjects for each group were: 5 cancer samples (5 subjects), 6 normal samples (4 patients) and 7 high-risk samples (5 subjects). After the initial inspection, one cancer sample (Sample 9) was excluded from the statistical analysis due to a poor RNA quality.
2009-04-07 | E-GEOD-15578 | biostudies-arrayexpress
Project description:Expression profiling identifies genes involved in neoplastic transformation of serous ovarian cancer
| PRJNA118973 | ENA
Project description:Ovarian cancer is one of the most deadly cancers accounting for only 3% of diagnosed cancers, but is the fifth leading cause of cancer deaths among woman; however, the progression of ovarian cancer is poorly understood. To study and further understand the early events that lead to epithelial derived ovarian cancer, we previously developed a cell model of progressive ovarian cancer. Mouse ovarian surface epithelial (MOSE) cells have undergone spontaneous transformation in cell culture and represent pre-neoplastic, non-tumorigenic to an aggressive malignant phenotype. Microarray analysis was performed with RNA isolated from different stages of MOSE cells to examine changes in gene expression as MOSE cells transition from a pre-neoplastic to a malignant state.
2011-03-03 | GSE24789 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.
| S-EPMC4686780 | biostudies-literature
Project description:PurposeWe investigated the evidence of recent positive selection in the human phototransduction system at single nucleotide polymorphism (SNP) and gene level.MethodsSNP genotyping data from the International HapMap Project for European, Eastern Asian, and African populations was used to discover differences in haplotype length and allele frequency between these populations. Numeric selection metrics were computed for each SNP and aggregated into gene-level metrics to measure evidence of recent positive selection. The level of recent positive selection in phototransduction genes was evaluated and compared to a set of genes shown previously to be under recent selection, and a set of highly conserved genes as positive and negative controls, respectively.ResultsSix of 20 phototransduction genes evaluated had gene-level selection metrics above the 90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal across these genes was found to be of similar magnitude to the positive control genes and much greater than the negative control genes.ConclusionsThere is evidence for selective pressure in the genes involved in retinal phototransduction, and traces of this selective pressure can be demonstrated using SNP-level and gene-level metrics of allelic variation. We hypothesize that the selective pressure on these genes was related to their role in low light vision and retinal adaptation to ambient light changes. Uncovering the underlying genetics of evolutionary adaptations in phototransduction not only allows greater understanding of vision and visual diseases, but also the development of patient-specific diagnostic and intervention strategies.
| S-EPMC3743458 | biostudies-literature