DIFFERENTIATION OF PANCREATIC-CARCINOMA INDUCED BY RETINOIC ACID OR SODIUM-BUTYRATE - A MORPHOLOGICAL AND MOLECULAR ANALYSIS OF 4 CELL-LINES

The antiproliferative and differentiation-inducing effects of all-tran s retinoic acid (RA) and sodium butyrate (SB) were investigated in fou r pancreatic ductal adenocarcinoma cell lines, two poorly differentiat ed ones (PT45 and PaTu-II), one moderately to poorly differentiated on e (Panc-1) and one highly differentiated one (A818-1). Treatment with 20 mu M RA resulted in moderate inhibition of cell growth in all cell lines, but clear evidence of cytodifferentiation (including elongated cell processes, increased rough endoplasmic reticulum, intensified imm unostaining for the mucin marker M1) was found only in PT45 and Panc-1 . These phenotypic changes were paralleled by upregulation of RAR (ret inoic acid receptor)-alpha and -gamma mRNA. SB (1 and 2 mM) treatment inhibited the cell growth of all cell lines much more prominently than RA. Cytodifferentiation was also largely restricted to PT45 and Panc- 1. A noticeable phenomenon was enhancement of the expression of the ne uroendocrine markers synaptophysin and Leu7 in Panc-1 cells. In conclu sion, it is evident that the original differentiation status of cells and their responsiveness to the agents are not clearly associated, and that RA responsiveness correlates with upregulation of RAR-alpha and mRNA.