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, Ada Sacchi

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1870-1879
Number of pages10
JournalCell Cycle
Volume7
Issue number12
Publication statusPublished - Jun 15 2008

Fingerprint

RNA Interference
Tumors
RNA
Mutant Proteins
Neoplasms
Proteins
Microarrays
Animals
Genes
Cells
p53 Genes
Information Systems
Human Activities
Down-Regulation
Animal Models
Growth

Keywords

  • Conditional RNAi
  • Gain of function
  • In vivo studies
  • Molecular targets
  • Mutant p53

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Bossi, G., Marampon, F., Maor-Aloni, R., Zani, B., Rotter, V., Oren, M., ... Sacchi, A. (2008). Conditional RNA interference in vivo to study mutant p53 oncogenic gain of function on tumor malignancy. Cell Cycle, 7(12), 1870-1879.

Conditional RNA interference in vivo to study mutant p53 oncogenic gain of function on tumor malignancy. / Bossi, Gianluca; Marampon, Francesco; Maor-Aloni, Revital; Zani, Bianca; Rotter, Varda; Oren, Moshe; Strano, Sabrina; Blandino, Giovanni; Sacchi, Ada.

In: Cell Cycle, Vol. 7, No. 12, 15.06.2008, p. 1870-1879.

Research output: Contribution to journalArticle

Bossi, G, Marampon, F, Maor-Aloni, R, Zani, B, Rotter, V, Oren, M, Strano, S, Blandino, G & Sacchi, A 2008, 'Conditional RNA interference in vivo to study mutant p53 oncogenic gain of function on tumor malignancy', Cell Cycle, vol. 7, no. 12, pp. 1870-1879.
Bossi G, Marampon F, Maor-Aloni R, Zani B, Rotter V, Oren M et al. Conditional RNA interference in vivo to study mutant p53 oncogenic gain of function on tumor malignancy. Cell Cycle. 2008 Jun 15;7(12):1870-1879.
Bossi, Gianluca ; Marampon, Francesco ; Maor-Aloni, Revital ; Zani, Bianca ; Rotter, Varda ; Oren, Moshe ; Strano, Sabrina ; Blandino, Giovanni ; Sacchi, Ada. / Conditional RNA interference in vivo to study mutant p53 oncogenic gain of function on tumor malignancy. In: Cell Cycle. 2008 ; Vol. 7, No. 12. pp. 1870-1879.
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