Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis

Rene Opavsky, Shih Yin Tsai, Martin Guimond, Anjulie Arora, Jana Opavska, Brian Becknell, Michael Kaufmann, Nathaniel A. Walton, Julie A. Stephens, Soledad A. Fernandez, Natarajan Muthusamy, Dean W. Felsher, Pierluigi Porcu, Michael A. Caligiuri, Gustavo Leone

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)15400-15405
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number39
DOIs
StatePublished - Sep 25 2007

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T-Lymphocytes
Carcinogenesis
Neoplasms
Apoptosis

Keywords

  • Cancer
  • Transcription

ASJC Scopus subject areas

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Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis. / Opavsky, Rene; Tsai, Shih Yin; Guimond, Martin; Arora, Anjulie; Opavska, Jana; Becknell, Brian; Kaufmann, Michael; Walton, Nathaniel A.; Stephens, Julie A.; Fernandez, Soledad A.; Muthusamy, Natarajan; Felsher, Dean W.; Porcu, Pierluigi; Caligiuri, Michael A.; Leone, Gustavo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 39, 25.09.2007, p. 15400-15405.

Research output: Contribution to journalArticle

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, G 2007, 'Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 39, pp. 15400-15405. https://doi.org/10.1073/pnas.0706307104
Opavsky, Rene ; Tsai, Shih Yin ; Guimond, Martin ; Arora, Anjulie ; Opavska, Jana ; Becknell, Brian ; Kaufmann, Michael ; Walton, Nathaniel A. ; Stephens, Julie A. ; Fernandez, Soledad A. ; Muthusamy, Natarajan ; Felsher, Dean W. ; Porcu, Pierluigi ; Caligiuri, Michael A. ; Leone, Gustavo. / Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 39. pp. 15400-15405.
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