Segnalo un evento che potrebbe interessarvi.
RP
-------- Messaggio Inoltrato --------
Oggetto: avviso Colloqui della Classe di Scienze, prof. Pier Giuseppe
Pelicci (08.06.2016)
Data: Fri, 27 May 2016 09:40:17 +0200
Mittente: Valeria Giuliani <valeria.giuliani(a)sns.it>
A: professori.sci(a)sns.it, professori.contratto.sci
<professori.contratto.sci(a)sns.it>, ricercatori.sci(a)sns.it,
ricercatori.td.sci(a)sns.it, Borsisti <borsisti(a)sns.it>,
assegnisti.sci(a)sns.it, Perfezionandi Scienze <phd.sci(a)sns.it>,
phd.extra.sci <phd.extra.sci(a)sns.it>, Studenti Scienze
<allievi.sci(a)sns.it>, allievi.extra.sci <allievi.extra.sci(a)sns.it>
CC: Classi <classi(a)sns.it>, Sito SNS <sitosns(a)sns.it>, Portineria
Carovana <portineria.carovana(a)sns.it>, Valeria Giusti
<valeria.giusti(a)sns.it>
*Colloqui della Classe di Scienze*
Mercoledì 8 giugno 2016
ore 15:00 __
__
_Scuola Normale Superiore_
Pisa
(Sala Azzurra)
*Prof. ****Pier Giuseppe Pelicci*
/((//Istituto Europeo di Oncologia (IEO), Milan, Italy – /
/Department of Oncology and Haemato-oncology, University of Milan, Italy)/
//
Terrà un seminario dal titolo:
*//*
*“**Regulation of self-renewal in cancer stem cells**”*
**
*Abstract:*
/“//Recent findings support the concept that cells with the properties
of stem cells (SC) are integral to the development and perpetuation of
several forms of human cancer, and that eradication of cancer stem cells
(CSC) may be essential to achieve cancer cure. However, direct proof of
these concepts is still lacking, mainly due the scarcity of appropriate
model systems.We have recently defined a number of CSC-specific
biological properties and underlying molecular mechanisms, using mouse
models of i) leukaemia, obtained by transgenic expression of the
PML-RAR, mutant NPM or AML1-ETO leukemia-associated oncogenes; and ii)
mammary tumor, obtained by transgenic expression of the ErbB2 oncogene.
We found that self-renewing divisions of CSCs are more frequent than
normal counterparts, unlimited and symmetric, thus contributing to
increasing numbers of SCs in tumoral tissues. SCs with targeted mutation
of the tumor suppressor p53 possess the same self-renewal properties of
cancer SCs, and their number increases progressively in the p53-null
pre-malignant mammary gland. We showed that p53 signaling is attenuated
in ErbB2-driven tumors, and that pharmacological re-activation of p53
induced restoration of asymmetric divisions in cancer SCs and tumor
growth reduction, without affecting rates of apoptosis or proliferation
on additional cancer cells. These data demonstrate that p53 regulates
polarity of cell division in mammary SCs and suggest that loss-of-p53 in
epithelial cancers favors symmetric divisions of CSCs, contributing to
tumor growth. As a further mechanisms of extended self-renewal in cancer
stem cells, we have demonstrated that up-regulation of the cell-cycle
inhibitor p21 is indispensable for maintaining self-renewal of leukaemia
SCs (LSCs). Expression of leukaemia-associated oncogenes in normal
hematopoietic SCs (HSCs) induces DNA damage and activates a
p21-dependent cellular response that, in turn, imposes cell-cycle
restriction and triggers repair of the damaged DNA. This effect of p21
prevents the physiological exhaustion of HSC self-renewal, which occurs
in time owing to accumulation of DNA damage, and confers an advantage to
HSCs when they hyper-proliferate, as it occurs during stress or after
full transformation (for example, in the LSCs), thus explaining the role
of p21 in the maintenance of the self-renewal potential of LSCs.
Finally, I will discuss unpublished data showing the contribution of
immune-surveillance to the elimination of DNA-damaged SCs, and the
underlying role of p21.”/
//
Tutti gli interessati sono invitati a partecipare.
Classe di Scienze Matematiche e Naturali
Valeria Giuliani
Scuola Normale Superiore
Servizio alla Didattica e Allievi
tel. 050 509260
Piazza dei Cavalieri, 7
56126 Pisa
E-mail: valeria.giuliani(a)sns.it <mailto:valeria.giuliani@sns.it>
E-mail: classi(a)sns.it <mailto:classi@sns.it>