Id
proteins antagonize basic helix-loop-helix
proteins, inhibit differentiation, and enhance cell proliferation. In this study we compared the expression of Id-1,
Id-2, and Id-3 in the normal pancreas, in
pancreatic cancer, and in
chronic pancreatitis (CP). Northern blot analysis demonstrated that all three Id
mRNA species were expressed at high levels in
pancreatic cancer samples by comparison with normal or CP samples.
Pancreatic cancer cell lines frequently coexpressed all three Ids, exhibiting a good correlation between Id
mRNA and
protein levels, as determined by immunoblotting with highly specific anti-Id
antibodies. Immunohistochemistry using these
antibodies demonstrated the presence of faint Id-1 and
Id-2 immunostaining in pancreatic ductal cells in the normal pancreas, whereas Id-3 immunoreactivity ranged from weak to strong. In the
cancer tissues, many of the
cancer cells exhibited abundant Id-1,
Id-2, and Id-3 immunoreactivity. Scoring on the basis of percentage of positive cells and intensity of immunostaining indicated that Id-1 and
Id-2 were increased significantly in the
cancer cells by comparison with the respective controls. Mild to moderate Id immunoreactivity was also seen in the ductal cells in the CP-like areas adjacent to these cells and in the ductal cells of small and interlobular ducts in CP. In contrast, in dysplastic and atypical papillary ducts in CP, Id-1 and
Id-2 immunoreactivity was as significantly elevated as in the
cancer cells. These findings suggest that increased Id expression may be associated with enhanced proliferative potential of
pancreatic cancer cells and of proliferating or dysplastic ductal cells in CP.