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Reports

Conditional RNA interference in vivo to study mutant p53 oncogenic gain of function on tumor malignancy

Gianluca Bossi, Francesco Marampon, Revital Maor-Aloni, Bianca Zani, Varda Rotter, Moshe Oren, Sabrina Strano, Giovanni Blandino and Ada Sacchi

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Mutant p53 proteins are thought to have acquired a "gain of function" (GOF) activity that mainly contributes to tumor aggressiveness. Previously we reported that constitutive downregulation of mutant p53 by RNA interference reduces the tumorigenicity of cancer cells in an animal model; however, effects of adaptation to long-term mutant p53 inhibition could not be excluded. To address this point, mimicking more physiological conditions, we now describe the establishment of a lentiviral-based system for conditional interference with mutant p53 expression. In vivo studies assessed the efficacy of conditional RNA interference in inhibiting gain of function activity of mutant p53 proteins by reducing tumor growth ability. Moreover by using this system, microarray data were validated in vitro and in vivo and putative mutant p53 target genes that may contribute to its gain of function effects in cancer were identified. Results are confirmatory that depletion of mutant p53 protein impacts on tumor malignancy and validated the inducible lentiviral-based system as an efficient tool to study the gain of function activity of human tumor derived p53 mutants.

Authors

Gianluca Bossi

Regina Elena Cancer Institute; Rome, Italy

Francesco Marampon

University of L'Aquila; L'Aquila, Italy

Revital Maor-Aloni

Weizmann Institute of Science; Rehovot Israel

Bianca Zani

University of L'Aquila; L'Aquila, Italy

Varda Rotter

Weizmann Institute of Science, Rehovot, Israel

Moshe Oren

Weizmann Institute of Science; Rehovot, Israel

Sabrina Strano

Regina Elena Cancer Institute; Rome, Italy

Giovanni Blandino

Regina Elena Cancer Institute; Rome, Italy

Ada Sacchi

Regina Elena Cancer Institute; Rome, Italy

Purchase article for $19

Subscribe to this journal for $129/year