The epidermal growth factor receptor is activated by a family of polyp
eptides that includes the growth factor amphiregulin (AR). Using North
ern blot analysis and the polymerase chain reaction, we now report tha
t AR mRNA is expressed in human pancreatic cancer cell lines, and that
this expression is enhanced in several of these cell lines by tetrade
canoyl phorbol acetate and transforming growth factor alpha. AR was al
so expressed in normal and malignant pancreatic tissues. However, in t
he normal pancreas, AR immunostaining was most evident in the nuclei o
f ductal cells. In contrast, in many carcinomas, AR was also present i
n the cytoplasm of the ductal-like cancer cells. Cytoplasmic localizat
ion of AR was associated with a more advanced clinical stage. These fi
ndings suggest that AR may contribute to aberrant activation of the ep
idermal growth factor receptor in human pancreatic cancer, and may enh
ance disease progression.