Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis. Proc Natl Acad Sci U S A 2007 Sep 25;104(39):15400-5
Date
09/21/2007Pubmed ID
17881568Pubmed Central ID
PMC2000495DOI
10.1073/pnas.0706307104Scopus ID
2-s2.0-34848837358 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
Deregulation of the Myc pathway and deregulation of the Rb pathway are two of the most common abnormalities in human malignancies. Recent in vitro experiments suggest a complex cross-regulatory relationship between Myc and Rb that is mediated through the control of E2F. To evaluate the functional connection between Myc and E2Fs in vivo, we used a bitransgenic mouse model of Myc-induced T cell lymphomagenesis and analyzed tumor progression in mice deficient for E2f1, E2f2, or E2f3. Whereas the targeted inactivation of E2f1 or E2f3 had no significant effect on tumor progression, loss of E2f2 accelerated lymphomagenesis. Interestingly, loss of a single copy of E2f2 also accelerated tumorigenesis, albeit to a lesser extent, suggesting a haploinsufficient function for this locus. The combined ablation of E2f1 or E2f3, along with E2f2, did not further accelerate tumorigenesis. Myc-overexpressing T cells were more resistant to apoptosis in the absence of E2f2, and the reintroduction of E2F2 into these tumor cells resulted in an increase of apoptosis and inhibition of tumorigenesis. These results identify the E2f2 locus as a tumor suppressor through its ability to modulate apoptosis.
Author List
Opavsky R, Tsai SY, Guimond M, Arora A, Opavska J, Becknell B, Kaufmann M, Walton NA, Stephens JA, Fernandez SA, Muthusamy N, Felsher DW, Porcu P, Caligiuri MA, Leone GAuthor
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Cell Cycle
Disease Progression
E2F1 Transcription Factor
E2F2 Transcription Factor
E2F3 Transcription Factor
Flow Cytometry
Gene Expression Regulation, Neoplastic
Humans
Lymphoma
Mice
Mice, Transgenic
Proto-Oncogene Proteins c-myc
T-Lymphocytes