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AssigneesInstitut National de la Sante et de la Recherche Medicale, Fondation Imagine, Assistance Publique-HôPitaux De Paris (Aphp), Université Paris Cité
InventorsChantal LAGRESLE-PEYROU, Marina CAVAZZANA, Isabelle ANDRE, Boris BESSOT, Nataël SOREL
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It was previously demonstrated that the RAC2 G12R mutation rapidly induced HSPCs cell death and hematopoiesis regulation. Now, the invention evaluated the impact of said mutation on three tumor cell lines: MDA-MB-231 (mammary gland adeno-carcinoma), HT29 (colorectal adenocarcinoma) and HepG2 (hepatocellular carcinoma). Briefly, cells were transduced with a lentiviral vector containing the green fluorescent protein (GFP) reporter cDNA (WPI) or a wild type form of RAC2 cDNA (WT) or a RAC2 mutated cDNA form (G12R). The inventors showed that the number of GFP+ cells is drastically lower in the G12R condition as compared to the WT and WPI conditions. The cell morphology and content are particularly disrupted. These observations were confirmed in a time-course proliferation assay performed on MDA-MB-231 and HT29 cell lines. Altogether, these data underlie the deleterious impact of the RAC2 G12R mutation on tumor cell lines proliferation.
A method of inducing cell death of a population of solid tumor cells comprising contacting said population with an effective amount of i) a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO:1 wherein the amino residue (G) at position 12 is mutated, or ii) a polynucleotide encoding for a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO:1 wherein the amino residue (G) at position 12 is mutated.
A method of treating a solid tumor in a patient in need thereof comprising administering to the patient a therapeutically effective amount of i) a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO:1 wherein the amino residue (G) at position 12 is mutated, or ii) a polynucleotide encoding for a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO:1 wherein the amino residue (G) at position 12 is mutated.
Dependencies are inferred from the claim text.