Università degli Studi di Udine OpenUniud - Archivio istituzionale delle tesi di dottorato
 

OpenUniud - Archivio istituzionale delle tesi di dottorato >
Udine Thesis Repository >
01 - Tesi di dottorato >

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10990/592

Autori: Viviani, Giulia
Supervisore afferente all'Università: BRANCOLINI, CLAUDIO
Centro di ricerca: DIPARTIMENTO SCIENZE MEDICHE E BIOLOGICHE - DSMB
Titolo: The MEF2-HDAC axis controls proliferation of mammary epithelial cells and acini formation in vitro
Abstract (in inglese): It is currently unclear how mammary epithelial cells organize in acinar structures and which genetic signals are involved in this process, even though distinct patterns of gene expression are considered the base to orchestrate fine tuned cellular decisions. MEF2 transcription factors are important players driving and controlling morphogenetic and differentiation processes in several districts of the body and their activity is highly and tightly regulated by class IIa HDACs. Despite described their central role during development, MEF2 factors and class IIa HDACs involvement in epithelial morphogenesis is still not characterized. Here, using 3D culture of human mammary MCF-10A acini as a model of study, we investigated the effect of the MEF2-HDAC pathway to elucidate its contribution in the epithelial side and its alteration by HER2, a known oncogene in breast cancer. We showed that MEF2-dependent transcription is up-regulated during acini formation and is coupled to a down-regulation of HDAC7, the most expressed class IIa HDAC in our model, which occurs independently from changes in mRNA levels, proteasome or autophagy mediated degradation. Pertubation of MEF2 activity, using shRNA lentiviral vectors or overexpressing a MEF2 or HDAC7 inducible form, affects cell proliferation controlling the expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A). Only in proliferating cells HDAC7 can bind the first intron of the CDKN1A gene, a region characterized by epigenetic markers of active promoters/enhancers. In cells overexpressing the HER2 oncogene 3D epithelial morphogenesis is altered, HDAC7 is continuously expressed and MEF2-dependent transcription is repressed. Importantly reactivation of MEF2 transcription in these cells, blocking HER2 activity or enhancing MEF2 function, reverted the proliferative defect and re-established normal acini morphogenesis
Parole chiave: HDCA7; HDAC4; HDAC5; MEF2A; MEF2D; CDKN1A; Cell cycle; Morphogenesis; Apoptosis; Breast cancer; HER2; Lapatinib; 3D culture
MIUR : Settore BIO/13 - Biologia Applicata
Lingua: eng
Data: 10-apr-2015
Corso di dottorato: Dottorato di ricerca in Scienze biomediche e biotecnologiche
Ciclo di dottorato: 27
Università di conseguimento titolo: Università degli Studi di Udine
Luogo di discussione: Udine
Citazione: Viviani, G. The MEF2-HDAC axis controls proliferation of mammary epithelial cells and acini formation in vitro. (Doctoral Thesis, Università degli Studi di Udine, 2015).
In01 - Tesi di dottorato

Full text:

File Descrizione DimensioniFormatoConsultabilità
Giulia Viviani PhD thesis.pdf6,35 MBAdobe PDFVisualizza/apri


Tutti i documenti archiviati in DSPACE sono protetti da copyright. Tutti i diritti riservati.


Segnala questo record su
Del.icio.us

Citeulike

Connotea

Facebook

Stumble it!

reddit


 

  ICT Support, development & maintenance are provided by CINECA. Powered on DSpace SoftwareFeedback CINECA