The MUC1 mucin regulates the tumorigenic properties of human esophageal adenocarcinomatous cells.

[esophageal adenocarcinoma]

MUC 1 is a membrane-bound mucin known to participate in tumor proliferation . It has been shown that MUC 1 pattern of expression is modified during esophageal carcinogenesis , with a progressive increase from metaplasia to adenocarcinoma . The principal cause of development of esophageal adenocarcinoma is gastro-esophageal reflux and MUC 1 was previously shown to be up-regulated by several bile acids present in reflux . In this report , our aim was thus to determine whether MUC 1 plays a role in biological properties of human esophageal cancer cells . For that , a stable MUC 1 -deficient esophageal cancer cell line was established using a shRNA approach . In vitro (proliferation , migration and invasion ) and in vivo (tumor growth following subcutaneous xenografts in SCID mice ) biological properties of MUC 1 -deficient cells were analyzed . Our results show that esophageal cancer cells lacking MUC 1 were less proliferative and had decreased migration and invasion properties . These alterations were accompanied by a decreased activity of NFKB p 65 , Akt and MAPK (p 44 /42 , JNK and p 38 ) pathways . MCM 6 and TSG 101 tumor -associated markers were also decreased . Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC 1 . Altogether , the data indicate that MUC 1 plays a key role in proliferative , migrating and invasive properties of esophageal cancer cells as well as in tumor growth promotion . MUC 1 mucin appears thus as a good therapeutic target to slow down esophageal tumor progression .