HER2-driven breast cancer suppression by the JNK signaling pathway.

ABSTRACT: The HER2⁺ subtype of human breast cancer is associated with the malignant transformation of luminal ductal cells of the mammary epithelium. The sequence analysis of tumor DNA identifies loss of function mutations and deletions of the MAP2K4 and MAP2K7 genes that encode direct activators of the JUN NH₂-terminal kinase (JNK). We report that in vitro studies of human mammary epithelial cells with CRISPR-induced mutations in the MAPK and MAP2K components of the JNK pathway caused no change in growth in 2D culture, but these mutations promoted epithelial cell proliferation in 3D culture. Analysis of gene expression signatures in 3D culture demonstrated similar changes caused by HER2 activation and JNK pathway loss. The mechanism of signal transd

SUBMITTER: Itah Z 

PROVIDER: S-EPMC9942916 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature