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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology breast cancer
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics RNA
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-IIF-2008
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
1066 CX AMSTERDAM
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.