RNA-Seq uncovers transcriptomic variations associated with the lethal phenotype conversion on LNCaP progression cell model
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View SamplesA genome-wide map of circular RNA in adult zebrafish.
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Gene expression profile of cervical and skin tissues from human papillomavirus type 16 E6 transgenic mice.
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View SamplesCopper-based chemotherapeutic compounds Casiopeinas, have been presented as able to promote selective programmed cell death in cancer cells, thus being proper candidates for targeted cancer therapy. DNA fragmentation and apoptosis -in a process mediated by reactive oxygen species- for a number of tumor cells, have been argued to be the main mechanisms. However, a detailed functional mechanism (a model) is still to be defined and interrogated for a wide variety of cellular conditions; before establishing settings and parameters needed for their wide clinical application.
Whole genome gene expression analysis reveals casiopeína-induced apoptosis pathways.
Cell line
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AP-2γ regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.
Cell line
View SamplesEstrogen receptor (ER) is key player in the progression of breast cancer. ER binds to DNA and mediates long-range chromatin interactions throughout the genome, but the underlying mechanism in this process is unclear. Here, we show that AP-2 motifs are highly enriched in the ER binding sites (ERBS) identified from the recent ChIA-PET of ER. More importantly, we demonstrate that AP-2 (also known as TFAP2C), a member of the AP-2 family which has been implicated in breast cancer oncogenesis, is recruited to chromatin in a ligand-independent manner and co-localized with ER binding events. Furthermore, pertubation of AP-2 expression disrupts ER DNA binding, long-range chromatin interactions, and gene transcription. Using ChIP-seq, we show that AP-2 and ER binding occurs in close proximity on a genome-wide scale. The majority of these shared genomic regions are also occupied by the pioneer factor, FoxA1. AP-2 is required for efficient FoxA1 binding and vice versa. Finally, we show that most ERBS associated with long-range chromatin interactions are co-localized with both AP-2 and FoxA1. Together, our results suggest AP-2 is an essential factor in ER-mediated transcription, primarily working together with FoxA1 to facilitate ER binding and long-range chromatin interactions.
AP-2γ regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.
Cell line
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Specimen part
View SamplesBreast cancer is a heterogeneous disease described in well-recognized biological subtypes. Particularly, gene expression profiling has revealed 5 intrinsic subtypes of breast cancer characterized by different biological and clinical features. The diversity of the intrinsic subtypes across human population has been limited described, and there is few information about the genomic architecture of breast tumors in Mexican or Hispanic populations. In this study, we performed PAM50 assay, based in Affymetrix microarray profiling of 128 fresh frozen tumors from Mexican Latino Hispanic population, to describe the overall distribution of subtypes, and characterize the relation to clinicopathologic characteristics. As well, we correlated the mRNA expression patterns with specific copy number alterations (CPA), in order to analyze their role in breast tumors. A total of 100 blood-tumor samples were assayed using Affymetrix 6.0 SNP arrays; segmentation analysis and GISTIC were performed to identify focal amplifications or deletions. The distribution of PAM50 intrinsic subtypes in our cohort was computed to be 44% luminal A, 20% luminal B, 12.0% HER2-enriched, 12% basal-like, and 12% normal-like. Study comparison with the literature mainly TCGA and METABRIC (most of the patients came from Caucasian population), as well as LACE (which describe a population study) show a similar distribution of the intrinsic subtypes within Hispanic and Caucasian populations. Interestingly, basal-like subtype is less represented than in African-American race. The sum of sensitivity and specificity between the clinicopathologic and intrinsic subtype categories across 4 groups (excluding normal-like) was 50% and 87.5%, respectively. Differentially expression profiles within the subtypes reveal a set of genes altered in each group with biological relevance to stablish the phenotypical characteristics of each subtype. Our analyses confirmed the already reported copy number data. Importantly, many of the copy number profiles correlated with mRNA subtype. With this analysis we can conclude that breast cancer intrinsic subtypes have been reproduced in Mexican population contributing to the description of the PAM50 subtypes among multiple ethnic groups based on a gene expression assay. Our observation based in the integrative genomic analysis of mRNA expression and CPA allowed us to define gene circuits and phenotypic characteristics that can explain the heterogeneity of breast cancer subtypes.
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View SamplesTriple negative breast cancer (TNBC) represents a challenging tumor type due to their poor prognosis and limited treatment options. It is well recognize that clinical and molecular heterogeneity of TNBC is driven in part by mRNA and lncRNAs. To stratify TNBCs, we profiled mRNAs and lncRNA in 158 adjuvant TNBC tumors using an Affymetrix microarray platform. Lehmann clustering analysis allowed us to identify TNBC subtypes featuring unique lncRNA expression patterns, disease free and overall survival rates and particular gene ontology enrichments (performed with GSEA algorithm).
Loss of function of miR-342-3p results in MCT1 over-expression and contributes to oncogenic metabolic reprogramming in triple negative breast cancer.
Specimen part
View SamplesTriple negative breast cancer (TNBC) represents a challenging tumor type due to their poor prognosis and limited treatment options. It is well recognize that clinical and molecular heterogeneity of TNBC is driven in part by mRNA and lncRNAs. To stratify TNBCs, we profiled mRNAs and lncRNA in 158 adjuvant TNBC tumors using an Affymetrix microarray platform. Lehmann clustering analysis allowed us to identify TNBC subtypes featuring unique lncRNA expression patterns, disease free and overall survival rates and particular gene ontology enrichments (performed with GSEA algorithm).
Loss of function of miR-342-3p results in MCT1 over-expression and contributes to oncogenic metabolic reprogramming in triple negative breast cancer.
Specimen part
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