Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-kinase p110delta

Class IA phosphoinositide 3-kinases (PI3Ks) regulate many cellular processes downstream of tyrosine kinases and Ras. Despite a clear impli-cation of PI3K in cancer, little is known about the distribution of the different PI3K isoforms in malignant cells. We screened a large panel of tissues and cell lines for expression of class IA PI3Ks, and document a ubiquitous expression of the p110 and p110 isoforms but a variable and more restricted tissue distribution of the p110 isoform. Originally found in WBCs, p110 was also detected in some nonhematopoietic cell types especially those of breast or melanocytic origin, both in the untransformed and transformed state. Isoform-specific neutralization of PI3K isoforms in breast cancer cell lines (by PI3K antibody microinjection or a p110-selective pharmacological inhibitor) demonstrated that p110 is the most important class IA PI3K in the regulation of epidermal growth factor-driven motility in vitro, controlling the directionality and, to a lesse