UP-REGULATION OF FAS (APO-1 CD95) LIGAND AND DOWN-REGULATION OF FAS EXPRESSION IN HUMAN ESOPHAGEAL CANCER/

Fas (APO-1/CD95) is a cell surface receptor that mediates apoptosis wh en it reacts with Fas ligand (FasL) or Fas antibody. In this study, we analyzed Fas and Fast expression in normal esophageal mucosa and esop hageal squamous cell carcinomas. Reverse transcriptase-PCR revealed th at Fas, soluble Fas, and Fast were expressed in all eight esophageal s quamous carcinoma cell lines analyzed. Furthermore, it was demonstrate d that Fast expressed in esophageal carcinoma cells is functional beca use coculture experiments using Fast-expressing TE-15 esophageal carci noma cells resulted in apoptosis of Jurkat T leukemia cells, which are sensitive to Fas-mediated apoptosis. Immunohistochemistry of Fas and Fast showed that they are constitutively expressed in normal esophagea l mucosa, Fast being predominantly in the basal and suprabasal layers, whereas Fas is in more differentiated layers, i.e., rows of polyhedra l cells of the intermediate layers and squamous cells forming the oute r layers. In 18 of 19 invasive esophageal squamous cell carcinomas, Fa st expression was found in >50% of tumor cells. In contrast, most tumo rs (15 of 19, 79%) either showed no Fas expression or showed expressio n in <5% of tumor cells. These alterations were already detected in dy splasia and carcinoma in situ. These results suggest that up-regulatio n of Fast and down-regulation of Fas expression are early and frequent events associated with the evolution of esophageal squamous cell carc inomas.