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Characterization of novel acting mechanisms of the Hepatocyte Growth Factor (HGF) in melanomagenesis: Bring into play the HGF transgenic animal model

Objective

Even though melanoma is the less frequent skin cancer, it is very likely to metastasise and lead to fatal consequences. It is worth it to take into consideration that, during the pass thirty years its incidence has increased significantly and that it has a very poor response to the currently available therapies. Different mouse models has been used to describe cutaneous melanoma, however, these tumours do not have the epidermal component that characterize the conventional human melanomas. Here, we use an ultra violet (UV) radiation, an environmental insult that has been epidemiologically related to the melanoma acquisition, to induced melanoma development in HGF transgenic mice.

The melanoma tumours raised in the HGF transgenic mice resembles human cutaneous melanoma with respect the aetiology, histopathology and molecular pathogenesis. Receptor tyrosine kinases (RTK) and human cancer are very closed related. Aberrant c-MET signalling (HGF receptor) has been implicated in the development and progression of a wide variety of human cancers, including melanoma. CDKN2A is the only tumour suppressor locus that has been unambiguously identified as a melanoma susceptibility gene. We also know from mouse models that Ras pathway activation is very important in melanoma development. However, the analysis of all the data suggest that the contribution of the HGF signalling in this mouse melanoma model can not be explained just with the Ras pathway activation.

The specific contributions made by the HGF signalling in these melanoma model that make this animal model so unique, are unknown. Briefly the objectives for the project are: (i) Isolation, purification and identification of differentially modified phopho-proteins in response to HGF in melanoma, (ii) Relevance and validation in the mouse melanoma model of the candidate or candidates chosen in the first part of the project in the tumour's development and progression, (iii) Correlation of the obtained data with human melanoma.

Call for proposal

FP6-2004-MOBILITY-12
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Funding Scheme

IRG - Marie Curie actions-International re-integration grants

Coordinator

FUNDACI¿INSTITUT DE RECERCA VALL D'HEBRON'
Address
Passieg Vall Dhebron 119-129
Barcelona
Spain