Project description:Human ovarian tissue cells positive for DDX4 on the surface were claimed to be of oogonial stem cell nature. In order to study DDX4 antibody positive putative oogonial stem cells, ovarian tissue cells were sorted into DDX4 antibody positive and negative populations and single cell RNA-seq was performed using Smart-seq2.
Project description:We have developed mouse models for serous epithelial ovarian cancer (SEOC) based on conditional inactivation of p53 and Rb tumor suppression (RB-TS) in combination with or without Brca1/2 following injection of adenovirus expressing Cre recombinase into the ovarian bursa. These models develop metastatic (Stage IV) disease with key histopathological features resembling human SEOC.To determine whether these mouse tumors resemble human SEOC at the molecular level, we conducted global gene expression analysis on 27 ovarian carcinomas and 3 pooled normal ovarian surface epithelium samples (single epithelial layer isolated from ovarian surface by laser capture). RNA was isolated from flash frozen ovarian tumors or from ovarian surface epithelial cells microdissected from frozen sections using PixCell IIe laser capture microdissection instrument.
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.
Project description:We have developed mouse models for serous epithelial ovarian cancer (SEOC) based on conditional inactivation of p53 and Rb tumor suppression (RB-TS) in combination with or without Brca1/2 following injection of adenovirus expressing Cre recombinase into the ovarian bursa. These models develop metastatic (Stage IV) disease with key histopathological features resembling human SEOC.To determine whether these mouse tumors resemble human SEOC at the molecular level, we conducted global gene expression analysis on 27 ovarian carcinomas and 3 pooled normal ovarian surface epithelium samples (single epithelial layer isolated from ovarian surface by laser capture).
Project description:Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment is understood. However, previous GEMMs of high-grade serous ovarian cancer (HGSOC) have had to utilize genetics rarely or never found in human HGSOC to yield ovarian cancer within the lifespan of a mouse. MYC, an oncogene, is amongst the most amplified genes in HGSOC, but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant negative mutant p53-R270H with a fallopian tube epithelium-specific promoter Ovgp1 to generate a new GEMM of HGSOC. Female mice developed lethal cancer at an average of 15.1 months. Histopathological examination of mice revealed HGSOC characteristics including nuclear p53 and nuclear MYC in clusters of cells within the fallopian tube epithelium and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the fallopian tube epithelium (FTE). Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Taken together, these results demonstrate the Myc and Trp53-R270H transgene was able to recapitulate many phenotypic hallmarks of HGSOC through the utilization of strictly human-mimetic genetic hallmarks of HGSOC. This new mouse model enables further exploration of ovarian cancer pathogenesis, particularly in the 50% of HGSOC which lack homology directed repair mutations. Histological and transcriptomic findings are consistent with the hypothesis that serous uterine cancer may originate from the fallopian tube epithelium.
Project description:We leverage RNA sequencing to identify the transcriptional changes assocaited with a TGFB1-induced epithelial-mesenchymal transition in the mouse ovarian surface epithelium
Project description:In order to evaluate pathways that drive the development of ovarian cancer, we compared Affymetrix expression profiles from normal ovarian surface epithelium to those from primary ovarian carcinomas.