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Content archived on 2024-05-29

Genetic screen for detecting genes expressed in embryonic stem calls that bypass immortalisatnio in primary cells


Current state-of-the-art in the research project Multicellular organisms have developed mechanisms to avoid deregulated growth and malignant transformation of proliferative cells. One such mechanism is cellular senescence, which stops proliferation afte r oncogenic alterations emerge. Primary cells directly excised from animal tissues can be explanted in vitro and cultured in different environments. One well-defined model of primary mouse cells are MEFs (mouse embrionic fibroblast). These cells, once e xplanted in vitro, undergo a limited number of divisions until they irreversibly arrest by a phenomenon known as replicative senescence (Hayflick, 1961; Dimri et al., 1995). Replicative senescence is evident by phenotypic and genotypic characteristics. Senescent cells acquire a large, flat morphology and they metabolically stop due to the inactivation of a series of genes involved in growth and cell cycle progression. Replicative senescence can be accelerated by overexpression of c-K-ras or PML (Ferbe yre et al., 2000) or bypassed due to the sobreexpression of specific oncogenes such as a dominant mutant of the p53 gene or mdm2 in murine cells or htert or mdm2 in human cells (Serrano et al., 1997, Carnero et al., 2001; Gil et al, manuscript in prepara tion, in this last work Dr. Lleonart has actively collaborated). Expected results and impact of the proposed project The impact of this project is very important in cancer research. The similarity between embryonic stem cells and cancer cells is that b oth of them grow indefinately. In contrast ES cells have a wild-type genome versus cancer cells that they contain several mutations in the DNA. Novel genes hopefully discovered from the genetic screen (wild-type genes), could be overexpressed in human tumors. The final goal of this project is to study if human tumors overexpress the genes discovered in the genetic screen.

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Paseo Vall d'Hebron 119-129

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