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.
Keywords
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Article info
Publication history
Published online: November 13, 2008
Accepted:
September 23,
2008
Received in revised form:
September 1,
2008
Received:
July 3,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
