[CvGmt News] avviso Colloqui della Classe di Scienze, prof. Pier Giuseppe Pelicci (08.06.2016)

[Valeria Giuliani]

*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 at sns.it
E-mail: classi at sns.it
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