Decreased expression of transforming growth factor alpha during differentiation of human pancreatic cancer cells.
The relationship between cell differentiation and transforming growth factor alpha (TGF-alpha) 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-alpha messenger RNA (mRNA) levels decreased, whereas the TGF-beta 1 mRNA levels remained unchanged. TGF-alpha was present in cells as proTGF-alpha, which decreased after butyrate treatment. Secretion of TGF-alpha 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-alpha mRNA level (500%), a not significant increase of TGF-beta 1 mRNA was observed. However, phorbol 12-myristate-13-acetate did not induce TGF-alpha synthesis or secretion. These data suggest that expression of TGF-alpha can be reduced in cancer cells; they also suggest the existence of a relationship between TGF-alpha expression and cell differentiation. In addition, the protein kinase C-induced TGF-alpha mRNA level was not followed by the increase of TGF-alpha biosynthesis, suggesting a translational control. Finally, the expression of TGF-alpha and -beta 1 messengers appears to be differently regulated.
Estival
A
A
INSERM U 151, Institut L. Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
Clerc
P
P
Vaysse
N
N
Tam
J P
JP
Clemente
F
F
D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014407:Tumor Cells, Cultured
D002087:Butyrates; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D020148:Butyric Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate