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Dataset Information

Expression data from mouse SEOC tumors

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Ludmila Szabova

PROVIDER: E-GEOD-46169 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer.

Szabova Ludmila L Yin Chaoying C Bupp Sujata S Guerin Theresa M TM Schlomer Jerome J JJ Householder Deborah B DB Baran Maureen L ML Yi Ming M Song Yurong Y Sun Wenping W McDunn Jonathan E JE Martin Philip L PL Van Dyke Terry T Difilippantonio Simone S

Cancer research 20120522 16

The majority of human high-grade serous epithelial ovarian cancer (SEOC) is characterized by frequent mutations in p53 and alterations in the RB and FOXM1 pathways. A subset of human SEOC harbors a combination of germline and somatic mutations as well as epigenetic dysfunction for BRCA1/2. Using Cre-conditional alleles and intrabursal induction by Cre-expressing adenovirus in genetically engineered mice, we analyzed the roles of pathway perturbations in epithelial ovarian cancer initiation and p ...[more]

PMID: 22617326

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Project description:Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells invaginate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 53) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 25 markers for GREL and other cells we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are separated from the stroma by a basal lamina. Around 130 days of gestation as the stroma expands laterally below the GREL cells on the surface thus establishing a sub-epithelial basal lamina and an epithelial-stromal interface, and it is at this stage that a mature surface epithelium develops from the GREL cells. The stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not invaginate into the ovary to form the granulosa cells of follicles. Microarray analysis of gene expression was conducted on different cell types cultured from fetal ovaries to identify possible markers of somatic cells during development. Two different cell types: Gonadal Ridge Epithelial-Like cells (n=2, 130 days gestation) and adult fibroblasts (n=1) were cultured from digested bovine fetal ovaries and gene expression compared with each other by Bovine Genome Affy array analysis in Partek Genomics Suite software, to identify possible markers of somatic cells during development.

Dataset Information

Expression data from mouse SEOC tumors

Publications

Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer.

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