Year: 2019
Type: article
Abstract: 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.
Source: Cell Reports
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: G1332332826, G1712026730, Genomic and Functional Identification of Chemotherapy Resistance Mechanisms in Small Cell Lung Cancer, G3995156439, G4004214011, G42679306, G5310623310, G5841304809, G595437086, G5954588232, G6238290905, G6276719192, DEFINING THE REGULATORY, NON-CODING, MUTATIONAL LANDSCAPE OF BREAST CANCER, G7647991836, G9000075027, G9000135348, G9000265189, G9000352744, Prolactin: mammary progenitors and tumor initiating cells in luminal carcinomas
OpenAlex ID: W2965972967