Unknown

Dataset Information

0

Type I to type II ovarian carcinoma progression: mutant Trp53 or Pik3ca confers a more aggressive tumor phenotype in a mouse model of ovarian cancer.


ABSTRACT: A dualistic pathway model of ovarian carcinoma (OvCA) pathogenesis has been proposed: type I OvCAs are low grade, genetically stable, and relatively more indolent than type II OvCAs, most of which are high-grade serous carcinomas. Endometrioid OvCA (EOC) is a prototypical type I tumor, often harboring mutations that affect the Wnt and phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathways. Molecular and histopathologic analyses indicate type I and II OvCAs share overlapping features, and a subset of EOCs may undergo type I?type II progression accompanied by acquisition of somatic TP53 or PIK3CA mutations. We used a murine model of EOC initiated by conditional inactivation of the Apc and Pten tumor suppressor genes to investigate mutant Trp53 or Pik3ca alleles as key drivers of type I?type II OvCA progression. In the mouse EOC model, the presence of somatic Trp53 or Pik3ca mutations resulted in shortened survival and more widespread metastasis. Activation of mutant Pik3ca alone had no demonstrable effect on the ovarian surface epithelium but resulted in papillary hyperplasia when coupled with Pten inactivation. Our findings indicate that the adverse prognosis associated with TP53 and PIK3CA mutations in human cancers can be functionally replicated in mouse models of type I?type II OvCA progression. Moreover, the models should represent a robust platform for assessment of the contributions of Trp53 or Pik3ca defects in the response of EOCs to conventional and targeted drugs.

SUBMITTER: Wu R 

PROVIDER: S-EPMC3620412 | biostudies-other | 2013 Apr

REPOSITORIES: biostudies-other

altmetric image

Publications

Type I to type II ovarian carcinoma progression: mutant Trp53 or Pik3ca confers a more aggressive tumor phenotype in a mouse model of ovarian cancer.

Wu Rong R   Baker Suzanne J SJ   Hu Tom C TC   Norman Kyle M KM   Fearon Eric R ER   Cho Kathleen R KR  

The American journal of pathology 20130401 4


A dualistic pathway model of ovarian carcinoma (OvCA) pathogenesis has been proposed: type I OvCAs are low grade, genetically stable, and relatively more indolent than type II OvCAs, most of which are high-grade serous carcinomas. Endometrioid OvCA (EOC) is a prototypical type I tumor, often harboring mutations that affect the Wnt and phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathways. Molecular and histopathologic analyses indicate type I and II OvCAs share overl  ...[more]

Similar Datasets

| S-EPMC7793521 | biostudies-literature
| S-EPMC6384094 | biostudies-literature
2023-07-14 | GSE236883 | GEO
| S-EPMC7565464 | biostudies-literature
| S-EPMC7718657 | biostudies-literature
| S-EPMC6043362 | biostudies-literature
| S-EPMC7396118 | biostudies-literature
| S-EPMC5152840 | biostudies-literature
| S-EPMC10948987 | biostudies-literature
| S-EPMC6148236 | biostudies-literature