The expression of the ΔNp73β isoform of p73 leads to tetraploidy

E. Marrazzo, S. Marchini, M. Tavecchio, T. Alberio, S. Previdi, E. Erba, V. Rotter, M. Broggini

Research output: Contribution to journalArticle

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Abstract

The p73 locus gene has a complex structure encoding a plethora of isoforms. The different ΔN truncated isoforms of p73 may exert different activities depending on the cellular context. The β isoform of ΔNp73 seems to have a particular pattern of action even if its role in cell cycle and mitosis is still under investigation. To gain further knowledge of ΔNp73β's function, we investigated the effects of its over-expression in tumour cellular models, using the tetracycline-inducible expression system. In the human lung carcinoma cell line H1299, ΔNp73β over-expression resulted in suppression of cell growth and in cell death. Surprisingly stable over-expression of ΔNp73β impaired the genomic stability of tumour cells, leading to the formation of tetraploid cells. The cells become enlarged and multinucleate, with incorrect mitotic figures, and died by apoptotic-independent pathways. Our data suggest that ΔNp73β-induced aberrant mitosis evades the control of the mitotic spindle assay checkpoint, leading to tetraploidy and cell death through mitotic catastrophe rather than apoptosis. The various C-terminal regions of ΔNp73 may influence the final cellular phenotype and we assume that the β one in particular could be important in both cell growth control and regulation of mitosis.

Original languageEnglish
Pages (from-to)443-453
Number of pages11
JournalEuropean Journal of Cancer
Volume45
Issue number3
DOIs
Publication statusPublished - Feb 2009

Fingerprint

Tetraploidy
Protein Isoforms
Mitosis
Cell Death
M Phase Cell Cycle Checkpoints
Genomic Instability
Growth
Tetracycline
Neoplasms
Cell Cycle
Apoptosis
Carcinoma
Phenotype
Cell Line
Lung
Genes

Keywords

  • ΔNp73
  • Cell cycle
  • Mitosis
  • TAp73
  • Tetraploidy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

The expression of the ΔNp73β isoform of p73 leads to tetraploidy. / Marrazzo, E.; Marchini, S.; Tavecchio, M.; Alberio, T.; Previdi, S.; Erba, E.; Rotter, V.; Broggini, M.

In: European Journal of Cancer, Vol. 45, No. 3, 02.2009, p. 443-453.

Research output: Contribution to journalArticle

Marrazzo, E, Marchini, S, Tavecchio, M, Alberio, T, Previdi, S, Erba, E, Rotter, V & Broggini, M 2009, 'The expression of the ΔNp73β isoform of p73 leads to tetraploidy', European Journal of Cancer, vol. 45, no. 3, pp. 443-453. https://doi.org/10.1016/j.ejca.2008.09.024
Marrazzo, E. ; Marchini, S. ; Tavecchio, M. ; Alberio, T. ; Previdi, S. ; Erba, E. ; Rotter, V. ; Broggini, M. / The expression of the ΔNp73β isoform of p73 leads to tetraploidy. In: European Journal of Cancer. 2009 ; Vol. 45, No. 3. pp. 443-453.
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