부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejca.2008.09.024 Byline: E. Marrazzo (a), S. Marchini (a), M. Tavecchio (b), T. Alberio (a), S. Previdi (a), E. Erba (b), V. Rotter (c), M. Broggini (a) Keywords: TAp73; [DELTA]Np73; Cell cycle; Mitosis; Tetraploidy Abstract: The p73 locus gene has a complex structure encoding a plethora of isoforms. The different [DELTA]N truncated isoforms of p73 may exert different activities depending on the cellular context. The [beta] isoform of [DELTA]Np73 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 [DELTA]Np73[beta]'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, [DELTA]Np73[beta] over-expression resulted in suppression of cell growth and in cell death. Surprisingly stable over-expression of [DELTA]Np73[beta] 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 [DELTA]Np73[beta]-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 [DELTA]Np73 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. Author Affiliation: (a) Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche 'Mario Negri', Via La Masa 19, 20156 Milan, Italy (b) Flow Cytometry Unit, Istituto di Ricerche Farmacologiche 'Mario Negri', Via La Masa 19, 20156 Milan, Italy (c) Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel Article History: Received 3 July 2008; Revised 1 September 2008; Accepted 23 September 2008