IDENTIFICATION OF A NOVEL GENETIC PROGRAM AT THE INITIATION OF COLON CANCER DEVELOPMENT.

As a result of a chronic inflammation or in response to the constitutive activation of the beta-catenin pathway, the generation of reactive oxygen species causes telomere attrition and triggers intestinal cell commitment into a senescence program. Nonetheless, such events are known to promote their neoplastic transformation, suggesting that the escape from oxidative stress-induced senescence favors the emergence of deleterious cells. By setting up an in vitro model, we demonstrated that the escape of human colonic epithelial cells from chronic inflammation-induced senescence lied on the activation of a specific genetic program. Immortalized human colonic epithelial cells (HCEC-hTERT) submitted to a chronic inflammation commit into a senescence program, until cells resume proliferation. We compared the gene expression profiles of the parental HCEC-hTERT cell line with cells that escaped from chronic inflammation-associated senescence, named Esc-Inf (from two independent experiments Esc-Inf A and Esc-Inf B) as well as HCEC-hTERT cells transduced with murine Zeb1 or Zeb2 (HCEC-Zeb1 and HCEC-Zeb2).