Involvement og MAGEA1 gene in tumorigensis
: In vivo and in vitro models

Traduction de l'intitulé de la thèse: Implication du gène MAGEA1 dans la tumorigenèse : Modèles in vivo et in vitro
  • Estelle WILLEMS

    Student thesis: Master types › Master en biochimie et biologie moléculaire et cellulaire

    Résumé

    MAGEA1, a member of type I melanoma antigens genes (MAGE), is only expressed in male germ cells and in cancer cells of several histological types. Some evidences support the hypothesis that MAGEA genes are expressed to provide a survival advantage to tumor cells.
    First, type I MAGE genes are able to inhibit the activity and decrease the level of the tumor suppressor p53. Secondly, MAGEA gene expression is associated with tumor invasiveness, lymph node metastasis, poor prognosis and advanced clinical stage. Moreover, MAGEA1 expression is also associated with increased chemoresistance. The purpose of my work was to study the involvement of MAGEA1 in tumor development using in vivo and in vitro models.
    The in vivo model involves the generation of transgenic mice expressing MAGEA1 ectopically in melanocytes. Expression of MAGEA1 transgene in mouse tissues was analyzed by quantitative RT-PCR. Preliminary results showed different levels of MAGEA1 transcripts in the skin of each mouse lineage, but not in the other examined tissues (testis, heart, liver and brain).
    The second goal of my project was to study the oncogenic functions of MAGEA1 in vitro. Using cell survival assays, a mechanism of chemoresistance conferred by MAGEA1 was detected in two different cell models (MCF-10A and MCF-7 cells) after treatment with etoposide, 5-fluorouracil and docetaxel. Complementary survival tests on Hep3B cells, a p53- deficient cell model, did not reveal chemoresistance in presence of MAGEA1 except after docetaxel treatment, a drug reported to work independently of p53 pathway. Forced expression of MAGEA1 by transduction induced an overexpression of ABC transporters
    mRNA in MCF-10A cells but not in Hep3B cells. As these transporters are mediators of chemoresistance, the induction of ABC transporters by MAGEA1 could represent a new mechanism of the chemoresistance induced by MAGEA1. In parallel, cell migration assays indicated that MAGEA1 also conferred a migratory advantage to MCF-10A cells, but not to Hep3B.
    la date de réponse2014
    langue originaleAnglais
    L'institution diplômante
    • Universite de Namur
    SuperviseurOlivier De Backer (Promoteur) & Elise Srour (Copromoteur)

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