MicroRNA-143/145 loss induces Ras signaling to promote aggressive Pten-deficient basal-like breast cancer.

ABSTRACT: The tumor suppressor PTEN is frequently inactivated in breast and other cancers; yet, germ-line mutations in this gene induce nonmalignant hamartomas, indicating dependency on additional cooperating events. Here we show that most tumors derived from conditional deletion of mouse pten in mammary epithelium are highly differentiated and lack transplantable tumor-initiating cells (TICs) capable of seeding new tumors following orthotopic injection of FACS-sorted or tumorsphere cells. A rare group of poorly differentiated tumors did harbor transplantable TICs. These transplantable tumors exhibited distinct molecular classification, signaling pathways, chromosomal aberrations, and mutational landscape, as well as reduced expression of microRNA-143/145 (miR-143/145). Stable knockdown of miR-143/1

SUBMITTER: Wang S 

PROVIDER: S-EPMC5543917 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature