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The estrogen receptor alpha (ERalpha) regulates gene expression by either direct binding to estrogen response elements or indirect tethering to other transcription factors on promoter targets. To identify these promoter sequences, we conducted a genome-wide screening with a novel microarray technique called ChIP-on-chip. A set of 70 candidate ERalpha loci(More)
The objective of this study was to identify and characterize a self-renewing subpopulation of human ovarian tumor cells (ovarian cancer-initiating cells, OCICs) fully capable of serial propagation of their original tumor phenotype in animals. Ovarian serous adenocarcinomas were disaggregated and subjected to growth conditions selective for self-renewing,(More)
We are beginning to appreciate the increasing complexity of mammalian gene structure. A phenomenon that adds an important dimension to this complexity is the use of alternative gene promoters that drive widespread cell type, tissue type or developmental gene regulation. Recent annotations of the human genome suggest that almost one half of the(More)
In breast cancer and normal estrogen target tissues, estrogen receptor-alpha (ERalpha) signaling results in the establishment of spatiotemporal patterns of gene expression. Whereas primary target gene regulation by ERalpha involves recruitment of coregulatory proteins, coactivators, or corepressors, activation of these downstream promoters by receptor(More)
Experimental and clinical evidence points to a critical role of progesterone and the nuclear progesterone receptor (PR) in controlling mammary gland tumorigenesis. However, the molecular mechanisms of progesterone action in breast cancer still remain elusive. On the other hand, micro RNAs (miRNAs) are short ribonucleic acids which have also been found to(More)
Many computational programs have been developed to identify enriched regions for a single biological ChIP-seq sample. Given that many biological questions are often asked to compare the difference between two different conditions, it is important to develop new programs that address the comparison of two biological ChIP-seq samples. Despite several programs(More)
BACKGROUND DNA methylation plays a very important role in the silencing of tumor suppressor genes in various tumor types. In order to gain a genome-wide understanding of how changes in methylation affect tumor growth, the differential methylation hybridization (DMH) protocol has been developed and large amounts of DMH microarray data have been generated.(More)
MicroRNAs are small non-coding RNAs involved in post-transcriptional regulation of gene expression. Due to the poor annotation of primary microRNA (pri-microRNA) transcripts, the precise location of promoter regions driving expression of many microRNA genes is enigmatic. This deficiency hinders our understanding of microRNA-mediated regulatory networks. In(More)
BACKGROUND Global profiling of in vivo protein-DNA interactions using ChIP-based technologies has evolved rapidly in recent years. Although many genome-wide studies have identified thousands of ERα binding sites and have revealed the associated transcription factor (TF) partners, such as AP1, FOXA1 and CEBP, little is known about ERα associated hierarchical(More)
BACKGROUND Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s) underlying the development of platinum resistance in(More)