Horizon Discovery Ltd., Cambridge, UK1, Departments of Cancer Signaling and Translational Oncology2, Bioinformatics3, Pathology4, Genentech, Inc., South San Francisco, CA, USA
Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy5
FIRC Institute of Molecular Oncology, Via Adamello 16, Milan, ZIP 20139, Italy6
Sponsored by Horizon Discovery Ltd.
Horizon Discovery’s proprietary rAAV GENESIS™ technology directly addresses this problem through the development of X-MAN™ isogenic cell lines. These models allow the interrogation of protein function without the problems associated with protein over-expression studies or genetically diverse cell line panels.
In order to investigate the effect that a PI3K mutation might have on tumour development, we employed isogenic cell lines derived from a ‘normal’ background. A PI3Kα (H1047R) mutation (commonly found in breast cancer patients) was knocked-in to produce a pair of MCF10A cell lines; parental cells that express wild-type PI3K or PI3Kα (H1047R) cells that express mutant PI3K1.
This investigation highlights how Horizon’s rAAV GENESIS technology can be applied, and reveals that introduction of a PI3K activating mutation can result in EMT switch and increased cell invasiveness.