Alternative NF1 Isoforms in RAS Deregulation and Breast Cancer Progression
Abstract
NF1 function is classically altered by gene deletion in breast cancer. An alternative-but-equally important mechanism of NF1 deficiency is defective mRNA processing whereby mutant mRNA transcripts directly or indirectly affect the stability of wild type transcripts. This delicate balance of mutant versus wild type transcript abundance can dramatically affect protein synthesis and, ultimately, RAS signaling fates. In cancer, dysregulation of alternative splicing promotes malignant progression and therapeutic resistance by altering the expression and function of tumor suppressors and oncogenes. Little is known about NF1-related mRNA processing or how alternative transcripts affect NF-related phenotypes such as breast cancer. Our goal is to define the genetic and isoform changes in NF1 that occur in breast cancer with the ultimate goal of identifying prognostic biomarkers and targeted therapeutic strategies for both female and male NF patients with breast cancer. Our hypothesis is that alternative RNA splicing of NF1 abrogates NF1 gene function and RAS regulation to promote breast cancer progression and therapeutic resistance. Our experimental approaches leverage innovative sequencing methods, our established rat model of Nf1-deficient breast cancer, and comprehensive analysis of breast cancer datasets.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1211442
Entities
People
- Matthew R. Steensma