AbstractMetastases are the final stage of cancer development and are responsible for many of the deaths from cancer. Recent studies have described the signaling pathways associated with metastatic phenotype. However, the actual involvement of these pathways in the initiation of metastasis is not always well understood. Another key feature of tumors is the presence of hypoxic areas caused by a lack of oxygen in the center. Hypoxia leads to the expression of genes promoting the formation of metastases and the repression of genes that prevent their development. Many studies of metastasis and / or the response to hypoxia have used DNA microarrays. However, they rarely have fully exploited this technique. As the data generated were made public, this work offers a re-analysis of these data sets to extract new information on the metastatic phenotype induced by hypoxia in several cancer cell lines, as well as validations of the hypotheses generated in silico. Three complementary approaches were developed that allowed the selection of 165 genes of interest. Among these 165 genes, 91 have already been described in the literature as being involved in cancer. Among which 41 are known to regulate the metastatic potential. Twenty genes were also described to be involved in the response to hypoxia. Finally, these 165 genes can be classified into 42 different signaling pathways, among which 12 are directly linked to cancer, while 5 others are related to proliferation and cell motility. 1000 negative controls consisting of 165 randomly selected genes were unable to provide such results. Surprisingly, 5 signaling pathways, in which are involved the 165 genes of interest are related to pathogen recognition and to phagocytosis. The expression profiles of 9 genes involved in one of the pathways of phagocytosis and one of the pathways of pathogen recognition were validated by real time RT-PCR. Migration tests were performed for three of these genes and two of them (PAK1 and CFL2) clearly show an involvement in cell migration providing new targets in the fight against this disease.
|Date of Award||27 Oct 2011|
|Supervisor||Eric DEPIEREUX (Supervisor), Carine MICHIELS (Co-Supervisor), Thierry ARNOULD (President), Xavier De Bolle (Jury) & Thierry Coche (Jury)|
- Puces à ADN
Méta-analyse de damiers à ADN pour l’identification de gènes impliqués dans l’hypoxie et causant le phénotype métastatique : mesure de leur expression dans des cellules de différents potentiels métastatiques en hypoxie et en normoxie
Pierre, M. (Author). 27 Oct 2011
Student thesis: Doc types › Doctor of Sciences