A genomic analysis (Comparative Genomic Hybridization) evidenced, among other chromosomic alterations, a microdeletion at 1p36.12 locus in 23% and 47% of colon adenomas and carcinomas, respectively. Among the 15 genes located in the deleted region, we focused on E2F2 gene involvedin various cellular processes. The Kaplan-Meier curve analysis showed that E2F2 deletion is associated with a better progression-free survival. To better understand the involvement of genes targeted by the microdeletion in colon tumors, we assessed the functional impact of the underexpression of E2F2 and of its direct neighbor gene ID3, coding for a dominant-negative repressor involved in cell differentiation. Our results indicated that E2F2 loss favors tumor growth and prevent metastatic spread. In collaboration with the biochemical team directed by the Pr Céline TARNUS, we started a pilotstudy to prove the anti-tumor potential of new chemical inhibitors highly selective of the aminopeptidase N.
The role of E2F2 and 1D3 transcription factors in tumor progression and therapeutic potential of targeting aminopeptidae N/CD13 in human colon cancer