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The expression of the DeltaNp73beta isoform of p73 leads to tetraploidy

Marrazzo, E; Marchini, S.; Tavecchio, M LU ; Alberio, T; Previdi, S; Erba, Eugenio; Rotter, V and Broggini, M (2009) In European Journal of Cancer 45(3). p.53-443
Abstract

The p73 locus gene has a complex structure encoding a plethora of isoforms. The different DeltaN truncated isoforms of p73 may exert different activities depending on the cellular context. The beta isoform of DeltaNp73 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 DeltaNp73beta'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, DeltaNp73beta over-expression resulted in suppression of cell growth and in cell death. Surprisingly stable over-expression of DeltaNp73beta impaired the genomic stability of... (More)

The p73 locus gene has a complex structure encoding a plethora of isoforms. The different DeltaN truncated isoforms of p73 may exert different activities depending on the cellular context. The beta isoform of DeltaNp73 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 DeltaNp73beta'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, DeltaNp73beta over-expression resulted in suppression of cell growth and in cell death. Surprisingly stable over-expression of DeltaNp73beta 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 DeltaNp73beta-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 DeltaNp73 may influence the final cellular phenotype and we assume that the beta one in particular could be important in both cell growth control and regulation of mitosis.

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Contribution to journal
publication status
published
keywords
Apoptosis, Cell Cycle, DNA-Binding Proteins, Gene Expression Regulation, Humans, Mitosis, Nuclear Proteins, Polyploidy, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Small Cell Lung Carcinoma, Tumor Suppressor Proteins, Journal Article, Research Support, Non-U.S. Gov't
in
European Journal of Cancer
volume
45
issue
3
pages
53 - 443
publisher
IFAC & Elsevier Ltd.
external identifiers
  • scopus:59149092149
ISSN
1879-0852
DOI
10.1016/j.ejca.2008.09.024
language
English
LU publication?
no
id
92b5d0a0-3d9d-4948-813d-a94c4d8c49a5
date added to LUP
2017-03-07 09:13:02
date last changed
2017-10-08 04:59:43
@article{92b5d0a0-3d9d-4948-813d-a94c4d8c49a5,
  abstract     = {<p>The p73 locus gene has a complex structure encoding a plethora of isoforms. The different DeltaN truncated isoforms of p73 may exert different activities depending on the cellular context. The beta isoform of DeltaNp73 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 DeltaNp73beta'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, DeltaNp73beta over-expression resulted in suppression of cell growth and in cell death. Surprisingly stable over-expression of DeltaNp73beta 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 DeltaNp73beta-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 DeltaNp73 may influence the final cellular phenotype and we assume that the beta one in particular could be important in both cell growth control and regulation of mitosis.</p>},
  author       = {Marrazzo, E and Marchini, S. and Tavecchio, M and Alberio, T and Previdi, S and Erba, Eugenio and Rotter, V and Broggini, M},
  issn         = {1879-0852},
  keyword      = {Apoptosis,Cell Cycle,DNA-Binding Proteins,Gene Expression Regulation,Humans,Mitosis,Nuclear Proteins,Polyploidy,Protein Isoforms,Reverse Transcriptase Polymerase Chain Reaction,Signal Transduction,Small Cell Lung Carcinoma,Tumor Suppressor Proteins,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {3},
  pages        = {53--443},
  publisher    = {IFAC & Elsevier Ltd.},
  series       = {European Journal of Cancer},
  title        = {The expression of the DeltaNp73beta isoform of p73 leads to tetraploidy},
  url          = {http://dx.doi.org/10.1016/j.ejca.2008.09.024},
  volume       = {45},
  year         = {2009},
}