Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression analysis of ovarian tumors from mice with knockout of DICER and PTEN

ABSTRACT: The cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer. RNA was isolated from the fallopian tube cancers of independent DKO mice and normal fallopian tubes of control mice and subjected to mRNA expression analysis using an Illumina platform (MouseWG-6 v2 Expression BeadChip).

ORGANISM(S): Mus musculus

SUBMITTER: Chad Creighton 

PROVIDER: E-GEOD-28720 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

High-grade serous ovarian cancer arises from fallopian tube in a mouse model.

Kim Jaeyeon J   Coffey Donna M DM   Creighton Chad J CJ   Yu Zhifeng Z   Hawkins Shannon M SM   Matzuk Martin M MM  

Proceedings of the National Academy of Sciences of the United States of America 20120213 10

Although ovarian cancer is the most lethal gynecologic malignancy in women, little is known about how the cancer initiates and metastasizes. In the last decade, new evidence has challenged the dogma that the ovary is the main source of this cancer. The fallopian tube has been proposed instead as the primary origin of high-grade serous ovarian cancer, the subtype causing 70% of ovarian cancer deaths. By conditionally deleting Dicer, an essential gene for microRNA synthesis, and Pten, a key negati  ...[more]

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