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Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-Kinase p110δ

Sawyer, Carol; Sturge, Justin; Bennett, Dorothy C.; O'Hare, Michael J.; Allen, William E.; Bain, Jennifer; Jones, Gareth E.; Vanhaesebroeck, Bart

Authors

Carol Sawyer

Dorothy C. Bennett

Michael J. O'Hare

William E. Allen

Jennifer Bain

Gareth E. Jones

Bart Vanhaesebroeck



Abstract

Class IA phosphoinositide 3′-kinases (PI3Ks) regulate many cellular processes downstream of tyrosine kinases and Ras. Despite a clear implication 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 p110α and p110β isoforms but a variable and more restricted tissue distribution of the p110δ isoform. Originally found in WBCs, p110δ 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 p110δ-selective pharmacological inhibitor) demonstrated that p110δ is the most important class IA PI3K in the regulation of epidermal growth factor-driven motility in vitro, controlling the directionality and, to a lesser extent, the speed of migration. In contrast, p110β was required for the direction but not the speed of migration, whereas p110α did not impact on either of these parameters. These results show a nonredundant function of PI3K isoforms downstream of the epidermal growth factor receptor and indicate that the presence of p110δ may confer breast cancer cells with selective migratory capacities. The potential clinical implications of p110δ expression in non-WBC-derived tumors are discussed.

Journal Article Type Article
Publication Date Apr 1, 2003
Print ISSN 0008-5472
Publisher American Association for Cancer Research
Peer Reviewed Peer Reviewed
Volume 63
Issue 7
Pages 1667-1675
APA6 Citation Sawyer, C., Sturge, J., Bennett, D. C., O'Hare, M. J., Allen, W. E., Bain, J., …Vanhaesebroeck, B. (2003). Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-Kinase p110δ. Cancer Research, 63(7), 1667-1675
Publisher URL http://cancerres.aacrjournals.org/content/63/7/1667
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