Lung cancer is the major cause of cancer deaths in Europe, and is claiming more deaths than breast, colon and prostate cancers combined. Early diagnosis allowing surgical resection with a 60 to 80% five years' survival is performed in less than 25% of the patients, stressing the need of identifying molecular biomarkers to improve early detection and therapies. Lung carcinogenesis is a multi-step process characterized by the accumulation of genetic alterations, due to exposure to carcinogens targeting genes controlling cell cycle, DNA repair, apoptosis, senescence, differentiation and cell migration.
ING genes (INhibitor of Growth) are candidate tumour suppressor genes which have been recently identified and characterized by us and others. They encode for proteins associated with cell cycle regulation, apoptosis, senescence and neoplastic transformation. Suppression of ING protein expression can be a critical step of the carcinogenesis process since inactivation of ING1 in preneoplastic cells results in the occurrence of tumours on nude mice (xenografts) and expression of ING1 protein is downregulated in numerous cancer types including breast, blood, esophageal, brain, bladder, stomach and liver cancers.
Our objectives aim at:
1) determining if ING genes may play a role in lung carcinogenesis and be biomarkers predictive of progression of pre-invasive and invasive lesions,
2) validating their interest for use as biomarkers in early diagnosis and/or targeted therapies,
3) understanding the mechanisms of their involvement in lung carcinogenesis.
We will conduct studies on human clinical samples as well as functional studies on cell lines using unique epithelial cells and fibroblast models and combining cell biology, molecular biology and biochemistry techniques. This integrated approach extending from molecular basis of tumour initiation and progression to clinical application in early diagnosis and targeted therapies, aims at decreasing lung cancer death.
Field of science
- /natural sciences/biological sciences/molecular biology
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
- /medical and health sciences/clinical medicine/cancer/prostate cancer
- /natural sciences/biological sciences/cell biology
- /medical and health sciences/clinical medicine/cancer/breast cancer
- /medical and health sciences/clinical medicine/cancer/liver cancer
Call for proposal
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