DECREASED EXPRESSION OF TRANSFORMING GROWTH-FACTOR ALPHA DURING DIFFERENTIATION OF HUMAN PANCREATIC-CANCER CELLS

The relationship between cell differentiation and transforming growth factor α (TGF-α) expression in human pancreatic cancer cells was analyzed in Capan 1 cells. These cells differentiate either spontaneously or after butyrate treatment. During differentiation (spontaneous or butyrate induced), TGF-α messenger RNA (mRNA) levels decreased, whereas the TGF-β1 mRNA levels remained unchanged. TGF-α was present in cells as proTGF-α, which decreased after butyrate treatment. Secretion of TGF-α was not found. Under the two conditions of differentiation, the membrane-bound protein kinase C activity was also reduced. Conversely, long-term phorbol ester treatment increased both membrane-bound protein kinase C activity (260%) and TGF-α mRNA level (500%), a not significant increase of TGF-β1 mRNA was observed. However, phorbol 12-myristate-13-acetate did not induce TGF-α synthesis or secretion. These data suggest that expression of TGF-α can be reduced in cancer cells; they also suggest the existence of a relationship between TGF-α expression and cell differentiation. In addition, the protein kinase C-induced TGF-α mRNA level was not followed by the increase of TGF-α biosynthesis, suggesting a translational control. Finally, the expression of TGF-α and -β1 messengers appears to be differently regulated. © 1992.