Objective
"Mutations of BRCA1 tumor suppressor gene account for 5-10% of hereditary breast cancers. Clinically, BRCA1-mutated cancers represent a unique subtype, with distinctive risk factors and poor prognosis. High-throughput technologies have identified genomic and transcriptomic signatures that are shared by sporadic and BRCA1-mutated breast tumors. BRCA1 mutations have been implicated in other types of tumors such as gastric, pancreatic and prostate cancers. A more detailed picture of BRCA1 tumor suppression functions is needed to design better tailored therapies for these aggressive cancers.
BRCA1-mutated tumors tend to accumulate mutations in PTEN and p53 tumor suppressor genes. The current model of BRCA1-related tumorigenesis posits that in BRCA1 mutation carries, the cell of origin bearing BRCA1 mutation at heterozygote status, undergoes loss of BRCA1 wild-type allele and loss or mutation of PTEN and p53 tumor suppressors. Although this intriguing model lacks in vivo evidence, it is widely accepted that PTEN and p53 gene inactivation are required for survival and transformation of BRCA1-mutated cells.
BRCA1, PTEN and p53 have been implicated in the regulation of intracellular levels of reactive oxygen species (ROS). Redox homeostasis derives from an imbalance between ROS generation and elimination. Redox homeostasis is crucial in the maintenance of cellular functions and it has implications in tumor development and sensitivity to anti-cancer therapies.
This study will investigate the role of PTEN and p53-regulated pathways in affecting the redox homeostasis of BRCA1 null cells. The activity of Nrf2 and FoxO transcription factors that regulate ROS and are related to BRCA1, PTEN and p53 will be considered. These signalling pathways will be analyzed in normal mouse mammary gland and in human breast cancers. Results will be translated into pre-clinical settings through orthoxenografts of primary human tumor samples and in vivo administration of chemotherapeutics."
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.
- medical and health sciences clinical medicine oncology prostate cancer
- medical and health sciences clinical medicine oncology breast cancer
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine physiology homeostasis
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IIF
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Funding Scheme
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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
08908 Hospitalet de Llobregat
Spain
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.