Project description:A series of gene expression measurements of uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene. Keywords: other
Project description:A series of gene expression measurements of normal myometrium and uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene. Keywords: other
Project description:A series of gene expression measurements of normal myometrium and uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene.
Project description:Analysis of genes regulated by RU486 (an progesterone antagonist) in human breast cancer T47D cells and human uterine leiomyoma smooth muscle cells. The hypothesis is that RU486 inhibits tumor growth by inactivating the transcription of multiple genes which trigger critical signaling pathways to induce tumorigenesis in both breast caner and uterine leomyoma. Tissue-specific and common patterns of gene regulation may determine the therapeutic effects of antiprogestins in uterine leiomyoma and breast cancer. Keywords: Expression profiling by array
Project description:Mutations in SPOP, the gene most frequently point-mutated in primary prostate cancer, are associated with a high degree of genomic instability and deficiency in homologous recombination repair of DNA but the underlying mechanisms. SPOP knockdown leads to spontaneous replication stress and impaired recovery from replication fork stalling. An SPOP interactome analysis shows that wild type (WT) SPOP but not mutant SPOP associates with multiple proteins involved in transcription, mRNA splicing and export. Consistent with the association of SPOP with transcription, splicing and RNA export complexes, the decreased expression of several components of the DNA damage response pathway occurs at the level of transcription.
Project description:Human histone deacetylase 3 (HDAC3) plays an important role in gene transcription in diseased human cells, such as leukemia. The t(8;21) chromosomal translocation is one of the most commonly observed genetic abnormalities associated with acute myeloid leukemia. This translocation generates the AML1-ETO fusion protein between the wild-type RUNX1 transcription factor and wild-type ETO transcriptional corepressor. To better understand the role of HDAC3 in t(8;21) leukemogenesis, the human HDAC3-containing complexes were isolated from stably-transfected HeLa cells by using anti-FLAG immunoprecipitation. The resulting complexes were resolved in SDS-PAGE. The components of the complexes were identified using LC-MS/MS. We report here that the human RUNX1 transcription is a component of the HDAC3 complexes. We demonstrate that HDAC3 and RUNX1 collaboratively repress AML1-ETO-mediated transcription. These results reveal new insight into how AML1-ETO, RUNX1, and HDAC3 crosstalk to deregulate gene transcription in t(8;21) leukemia cells.
Project description:Postnatal development of the uterus involves specification of undifferentiated epithelium into uterine-type epithelium. That specification is regulated by stromal-epithelial interactions as well as intrinsic cell-specific transcription factors and gene regulatory networks. This study utilized mouse genetic models of Esr1 deletion, endometrial epithelial organoids (EEO), and organoid-stromal co-cultures to decipher the role of Esr1 in uterine epithelial development. Organoids derived from wild-type (WT) mice developed a normal single layer of columnar epithelium. In contrast, EEO from Esr1 null mice developed a multilayered stratified squamous type of epithelium with basal cells. Co-culturing Esr1 null epithelium with WT uterine stromal fibroblasts inhibited basal cell development. Of note, estrogen treatment of EEO-stromal co-cultures and Esr1 conditional knockout mice increased basal epithelial cell markers. Collectively, these findings suggest that Esr1 regulates uterine epithelium lineage plasticity and homeostasis and loss of ESR1 promotes altered luminal-to-basal differentiation driven by ESR1-mediated paracrine factors from the stroma.