1. ¹Department of Microbiology and Immunology and Tulane Cancer Center, Tulane University Health Sciences Center, New Orleans, LA, USA
2. ²Department of Molecular Virology and Microbiology and Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX, USA

Correspondence: Dr LS Levy, Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Avenue SL-38, New Orleans, LA 70112, USA. E-mail: llevy@tulane.edu

Received 20 August 2006; Revised 19 March 2007; Accepted 1 April 2007; Published online 7 May 2007.

Abstract

p101, the regulatory subunit of phosphatidylinositol-3-kinase-gamma (PI3K), was recently reported as a common site of retroviral insertion in T-cell lymphomas induced in mice by MoFe2-MuLV, a unique recombinant gammaretrovirus. The common interruption of p101 by retroviral integration suggests that the locus encodes an oncogene whose altered expression is related to the induction of T-cell malignancy. To examine a possible role in the malignant process, p101 was overexpressed in human T-cell lines Molt-4 and Jurkat. Transient overexpression of p101 induced apoptosis in recipient cells; however, stable expression could be established in cells that expressed moderate levels of p101. Constitutive p101 overexpression in those cells conferred significant protection against ultraviolet-induced apoptosis. Protection against apoptotic induction was attributed to p101-mediated activation of the Akt pathway. Constitutive overexpression of p101 enhanced the activity of p110 and further sensitized it to activation upon stimulation of G protein-coupled receptor. These findings are the first to implicate altered expression of p101 in malignancy, specifically in T-cell lymphoma. The findings further provide insight into the regulation of p110, indicating that the stoichiometry of p110 and p101 are important in regulating PI3K signaling.