| First Author | Campbell KM | Year | 2019 |
| Journal | Cell Rep | Volume | 28 |
| Issue | 6 | Pages | 1526-1537.e4 |
| PubMed ID | 31390566 | Mgi Jnum | J:288429 |
| Mgi Id | MGI:6432162 | Doi | 10.1016/j.celrep.2019.06.098 |
| Citation | Campbell KM, et al. (2019) A Spontaneous Aggressive ERalpha+ Mammary Tumor Model Is Driven by Kras Activation. Cell Rep 28(6):1526-1537.e4 |
| abstractText | The NRL-PRL murine model, defined by mammary-selective transgenic rat prolactin ligand rPrl expression, establishes spontaneous ER+ mammary tumors in nulliparous females, mimicking the association between elevated prolactin (PRL) and risk for development of ER+ breast cancer in postmenopausal women. Whole-genome and exome sequencing in a discovery cohort (n = 5) of end-stage tumors revealed canonical activating mutations and copy number amplifications of Kras. The frequent mutations in this pathway were validated in an extension cohort, identifying activating Ras alterations in 79% of tumors (23 of 29). Transcriptome analyses over the course of oncogenesis revealed marked alterations associated with Ras activity in established tumors compared with preneoplastic tissues; in cell-intrinsic processes associated with mitosis, cell adhesion, and invasion; as well as in the surrounding tumor environment. These genomic analyses suggest that PRL induces a selective bottleneck for spontaneous Ras-driven tumors that may model a subset of aggressive clinical ER+ breast cancers. |
