MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel.

<h4>Background</h4>The role of the MYC oncogene in the apoptotic pathways is not fully understood. MYC has been reported to protect cells from apoptosis activation but also to sensitize cells to apoptotic stimuli. We have previously demonstrated that the down-regulation of Myc protein ac...

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Autores principales:	Giuliana Gatti, Giovanna Maresca, Manuela Natoli, Fulvio Florenzano, Angelo Nicolin, Armando Felsani, Igea D'Agnano
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7377676b868d4f5283c5ca3a97a2249c
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spelling	oai:doaj.org-article:7377676b868d4f5283c5ca3a97a2249c2021-11-25T06:22:50ZMYC prevents apoptosis and enhances endoreduplication induced by paclitaxel.1932-620310.1371/journal.pone.0005442https://doaj.org/article/7377676b868d4f5283c5ca3a97a2249c2009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19421315/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The role of the MYC oncogene in the apoptotic pathways is not fully understood. MYC has been reported to protect cells from apoptosis activation but also to sensitize cells to apoptotic stimuli. We have previously demonstrated that the down-regulation of Myc protein activates apoptosis in melanoma cells and increases the susceptibility of cells to various antitumoral treatments. Beyond the well-known role in the G1-->S transition, MYC is also involved in the G2-M cell cycle phases regulation.<h4>Methodology/principal findings</h4>In this study we have investigated how MYC could influence cell survival signalling during G2 and M phases. We used the microtubules damaging agent paclitaxel (PTX), to arrest the cells in the M phase, in a p53 mutated melanoma cell line with modulated Myc level and activity. An overexpression of Myc protein is able to increase endoreduplication favoring the survival of cells exposed to antimitotic poisoning. The PTX-induced endoreduplication is associated in Myc overexpressing cells with a reduced expression of MAD2, essential component of the molecular core of the spindle assembly checkpoint (SAC), indicating an impairment of this checkpoint. In addition, for the first time we have localized Myc protein at the spindle poles (centrosomes) during pro-metaphase in different cell lines.<h4>Conclusions</h4>The presence of Myc at the poles during the prometaphase could be necessary for the Myc-mediated attenuation of the SAC and the subsequent induction of endoreduplication. In addition, our data strongly suggest that the use of taxane in antitumor therapeutic strategies should be rationally based on the molecular profile of the individual tumor by specifically analyzing Myc expression levels.Giuliana GattiGiovanna MarescaManuela NatoliFulvio FlorenzanoAngelo NicolinArmando FelsaniIgea D'AgnanoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 5, p e5442 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giuliana Gatti Giovanna Maresca Manuela Natoli Fulvio Florenzano Angelo Nicolin Armando Felsani Igea D'Agnano MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel.
description	<h4>Background</h4>The role of the MYC oncogene in the apoptotic pathways is not fully understood. MYC has been reported to protect cells from apoptosis activation but also to sensitize cells to apoptotic stimuli. We have previously demonstrated that the down-regulation of Myc protein activates apoptosis in melanoma cells and increases the susceptibility of cells to various antitumoral treatments. Beyond the well-known role in the G1-->S transition, MYC is also involved in the G2-M cell cycle phases regulation.<h4>Methodology/principal findings</h4>In this study we have investigated how MYC could influence cell survival signalling during G2 and M phases. We used the microtubules damaging agent paclitaxel (PTX), to arrest the cells in the M phase, in a p53 mutated melanoma cell line with modulated Myc level and activity. An overexpression of Myc protein is able to increase endoreduplication favoring the survival of cells exposed to antimitotic poisoning. The PTX-induced endoreduplication is associated in Myc overexpressing cells with a reduced expression of MAD2, essential component of the molecular core of the spindle assembly checkpoint (SAC), indicating an impairment of this checkpoint. In addition, for the first time we have localized Myc protein at the spindle poles (centrosomes) during pro-metaphase in different cell lines.<h4>Conclusions</h4>The presence of Myc at the poles during the prometaphase could be necessary for the Myc-mediated attenuation of the SAC and the subsequent induction of endoreduplication. In addition, our data strongly suggest that the use of taxane in antitumor therapeutic strategies should be rationally based on the molecular profile of the individual tumor by specifically analyzing Myc expression levels.
format	article
author	Giuliana Gatti Giovanna Maresca Manuela Natoli Fulvio Florenzano Angelo Nicolin Armando Felsani Igea D'Agnano
author_facet	Giuliana Gatti Giovanna Maresca Manuela Natoli Fulvio Florenzano Angelo Nicolin Armando Felsani Igea D'Agnano
author_sort	Giuliana Gatti
title	MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel.
title_short	MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel.
title_full	MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel.
title_fullStr	MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel.
title_full_unstemmed	MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel.
title_sort	myc prevents apoptosis and enhances endoreduplication induced by paclitaxel.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/7377676b868d4f5283c5ca3a97a2249c
work_keys_str_mv	AT giulianagatti mycpreventsapoptosisandenhancesendoreduplicationinducedbypaclitaxel AT giovannamaresca mycpreventsapoptosisandenhancesendoreduplicationinducedbypaclitaxel AT manuelanatoli mycpreventsapoptosisandenhancesendoreduplicationinducedbypaclitaxel AT fulvioflorenzano mycpreventsapoptosisandenhancesendoreduplicationinducedbypaclitaxel AT angelonicolin mycpreventsapoptosisandenhancesendoreduplicationinducedbypaclitaxel AT armandofelsani mycpreventsapoptosisandenhancesendoreduplicationinducedbypaclitaxel AT igeadagnano mycpreventsapoptosisandenhancesendoreduplicationinducedbypaclitaxel
_version_	1718413807006515200

MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel.

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