ALTERED EXPRESSION OF INSULIN-LIKE-GROWTH-FACTOR-II RECEPTOR IN HUMANPANCREATIC-CANCER

The insulin-like growth factor-II (IGF-II) receptor (IGF-IIR) is a sin gle-chain transmembrane protein identical to the mannose-6-phosphate r eceptor. In the present study we examined IGF-IIR expression in normal and cancerous human pancreatic tissues. In the normal pancreas, moder ately strong IGF-IIR immunoreactivity was present in the cytoplasm of islet cells, and mild cytoplasmic immunoreactivity was evident occasio nally in ductal and acinar cells. Some ductal cells also exhibited nuc lear IGF-IIR immunoreactivity. In the pancreatic cancers, regions of s trong IGF-IIR immunoreactivity were present in the duct-like cancer ce lls within the tumor mass, often exhibiting nuclear localization. Expr ession of IGF-IIR mRNA in the cancer cells was confirmed by in situ hy bridization. By comparison with normal pancreatic tissues, 7 of 12 pan creatic cancers exhibited a 5.6-fold increase in IGF-IIR mRNA levels, whereas in 3 cancers the IGF-IIR transcript was below the level of det ection. Furthermore, all six tested cultured human pancreatic cancer c ell lines expressed the IGF-IIR mRNA transcript. Our data indicate tha t IGF-IIR is overexpressed in a significant number of human pancreatic cancers, where it has a tendency to localize in the nucleus, and rais e the possibility that IGF-IIR may contribute to the pathobiology of p ancreatic cancer.