Differentially expressed genes between normal and cancer tissues of the pancreas were investigated using differential display. Consequently, we identified a fragment cDNA that was expressed in the normal tissue but was rarely expressed in the cancer tissue. This cDNA was screened in cDNA library prepared from the normal pancreatic tissue by rapid amplification of cDNA ends (5'RACE). 859 bp of cDNA was cloned and sequenced, and the inferred amino acid sequence was found to encode a G protein gamma subunit with 98% homology to cow G protein gamma 7 and complete homology to human G protein gamma 7. The decreased expression of the G protein gamma 7 was confirmed by Northern blot assay in twelve pancreatic malignancies which included nine duct cell carcinomas, two cystoadenocarcinomas and one blastoma. Reverse transcriptase (RT)-polymerase chain reaction (PCR) assay showed no expression of G protein gamma 7 in five of six pancreatic carcinoma cell lines and two pancreatic cancer tissues. Immunohistochemical analysis also displayed positive staining in the normal tissue but no staining in the cancer tissue. The findings demonstrated that the reduced or suppressed expression of human G-protein gamma 7 may play an important role in pancreatic carcinogenesis.