BREAST STEM CELLS

The role of Polycomb genes in normal stem cell and breast cancer stem cell self-renewal and maintenance

 Coordinatore STICHTING HET NEDERLANDS KANKER INSTITUUT 

 Organization address address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX

contact info
Titolo: Dr.
Nome: Henri
Cognome: Van Luenen
Email: send email
Telefono: 31205122097
Fax: 31206691383

 Nazionalità Coordinatore Netherlands [NL]
 Totale costo 167˙157 €
 EC contributo 167˙157 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-IIF-2008
 Funding Scheme MC-IIF
 Anno di inizio 2009
 Periodo (anno-mese-giorno) 2009-03-01   -   2009-12-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    STICHTING HET NEDERLANDS KANKER INSTITUUT

 Organization address address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX

contact info
Titolo: Dr.
Nome: Henri
Cognome: Van Luenen
Email: send email
Telefono: 31205122097
Fax: 31206691383

NL (AMSTERDAM) coordinator 167˙157.36

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

maintenance    stem    cells    mice    genes    bmi    normal    cancer    ezh    women    group    polycomb    tumor    approximately    chemotherapy    breast    cell    mammary   

 Obiettivo del progetto (Objective)

'Breast cancer is the most common malignancy of women in developed nations. Approximately 1 in 9 women will be diagnosed with breast cancer and many will receive chemotherapy and achieve long-term cancer control. However, in approximately one-third of these women, cancer will recur. This is thought to be due to the presence of chemotherapy-resistant ‘breast cancer stem cells’. Two Polycomb-group proteins, Bmi1 and Ezh2, are frequently over-expressed in breast cancer, suggesting that these epigenetic regulators may play a role in breast tumorigenesis. Interestingly, Bmi1 and Ezh2 are also known to be involved in the maintenance of adult stem cells and in normal mammary gland development. Based on these observations, we postulate that Ezh2 and Bmi1 are critical for maintaining mammary stem cell identity and that mutations leading to the continuous expression of these Polycomb-group genes contribute to the generation of breast cancer stem cells. This project will study the parallels between the role of Polycomb genes in normal mammary stem cell maintenance and their role in breast cancer. We will use novel transgenic mice that express doxycycline-regulatable short hairpin (sh)RNAs to Bmi1 and Ezh2 alone, or in combination with established mammary tumor models that closely resemble human disease. Using these mice, we will investigate whether a) knockdown of Bmi1 and Ezh2 causes a regression of the normal and/or cancer stem cell compartment and b) whether this can be exploited to eradicate mammary tumors. Understanding the way in which Ezh2 and Bmi1 exert their effects may lead to novel targeted therapies for breast cancers, which may lead to the eradication of those cells that have the capacity to initiate tumor recurrence. We are confident that the proposed studies, many of which are already well in progress, will provide new insight into the factors that contribute to cancer initiation and maintenance and will have important implications for cancer treatment.'

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