P53 Deficiency Accelerate Esophageal Epithelium Intestinal Metaplasia Malignancy

Barrett's esophagus (BE) is a precancerous lesion of esophageal adenocarcinoma (EAC). It is a pathological change in which the squamous epithelium distal esophagus is replaced by columnar epithelium. Loss of is involved in the development of BE and is taken as a risk factor for the progression. We established a HET1A cell line with stably knockdown by adenovirus vector infection, followed by 30 days of successive acidic bile salt treatment. MTT, transwell assay, and wound closure assay were applied to assess cell proliferation and migration ability. The expression of key factors was analyzed by RT-qPCR, western blotting and immunohistochemical staining. Our data show that the protein expression level of reduced after exposure to acidic bile salt treatment, and the deficiency favors the survival of esophageal epithelial cells to accommodate the stimulation of acidic bile salts. Furthermore, exposure to acidic bile salt decreases cell adhesions by repressing the signaling pathway and activating in -deficient esophageal cells. In EAC clinical samples, protein expression is positively correlated with that of and and negatively correlated with protein expression levels. These findings elucidate the role of in the formation of BE, explain the mechanism of deficiency as a higher risk of progression for BE formation, and provide potential therapeutic targets for EAC.