Neurotensin receptor-1 mRNA analysis in normal pancreas and pancreatic disease

By autoradiography, neurotensin (NT) binding is specifically detectable in pancreatic cancer, but not in the normal pancreas, chronic pancreatitis (CP ), or other pancreatic disorders. In the present study, we investigated whe ther this is due to NT receptor-1 (NTR-1) mRNA up-regulation and whether NT R-I mRNA could also be used as a specific diagnostic marker and treatment t arget in pancreatic cancer. Fifteen normal pancreas tissue samples, 20 CP samples, and 30 pancreatic ca ncer samples were studied. Expression and localization of NTR-1 mRNA uas in vestigated by Northern blot analysis and in situ hybridization. Furthermore , consecutive tissue sections were analyzed for NTR-1 mRNA expression and N T binding. By Northern blot analysis, NTR-I mRNA expression was 4.4-fold (P < 0.01) an d 3.0-fold (P < 0.01) higher in pancreatic cancer and CP tissue samples, re spectively? compared with normal controls, There was no difference in NTR-1 mRNA levels between CP and cancer samples (P > 0.05), In pancreatic cancer , the NTR-1 mRNA, levels were higher in advanced tumor stage (stages III an d IV) than early tumor stage (stages I and II; P < 0.05), but no difference was found between well moderately differentiated (grades 1 and 2) and poor ly differentiated/undifferentiated cancers (grades 3 and 4; P > 0.05), By i n situ hybridization, NTR-I mRNA signals were weakly present in the cytopla sm of acinar and ductal cells of the normal pancreas, Moderate to intense N TR-I mRNA signals were present in the cytoplasm of acinar cells dedifferent iating into tubular complexes and degenerating acinar cells of CP samples. In the cancer samples, NTR-1 mRNA was moderately to intensely expressed in the cytoplasm of cancer cells. When on consecutive tissue sections NTR-1 mR NA expression was compared with the presence of NTR-I, measured by receptor autoradiography, a correlation was found in carcinomas but not in CP sampl es, In which no receptors were detectable by autoradiography. The enhanced expression of NTR-1 mRNA in pancreatic cancer cells further su ggests that neuroendocrine hormones might modulate pancreas cancer cell beh avior. However, its relatively high levels in CP excludes NTR-1 mRNA as a s pecific parameter for pancreatic cancer and for the differentiation of panc reatic cancer from CP.