Figure 9. Models for oncogenic cooperation between PTEN deficiency and miR-143/145 loss or RAS-pathway activation.

(A) A model of oncogenic cooperation between miR-143/145 and pten loss in mouse mammary tumors, leading to highly tumorigenic, transplantable tumor-initiating cells (TICs). Additional alterations such as those identified by array-based comparative genomic hybridization and exome sequencing may further cooperate with pten–miR-143/145 loss to induce aggressive poorly differentiated adenocarcinomas (PDAs). PTEN loss promotes cancer via PIP₃-dependent and PIP₃-independent mechanisms. (B) A model of oncogenic cooperation between miR-143/145 and PTEN loss in human breast cancer (BC). miR-143/145 and other genetic alterations induce RAS signaling. PTEN-low/miR-143/145–low and PTEN-low/RAS-pathway-high triple-negative BC (TNBC) patients should be identified and prioritized for aggressive therapy. AME, adenomyoepithelioma.