| Recent the morbidity of pancreatic adenocarcinoma has a tendency to be increasing. It's well know that the malignancy of pancreatic adenocarcinoma is much higher than any other alimentary tract carcinomas, it's easy for pancre- atic adenocarcinoma to metaslasize, no validity diagnosis is found for this dis- ease, with a high relapse after operation, all of which contribate to the poor prognosis of pancreatic adenocarcinoma. Now, the study of the genes which are associated with the ctevelopment of carcinoma is becoming the hot spot in oncology field. The aim of this study is (i) to explore the change regularity of the FHIT gene in pancreatic adenocarcinoma and their adjacent tissues, (ii) determine the effect on cell growth and tumorigenicity of FHIT gene in 1990 pancreatic adeno careimoma cell line (iii) to probe the mechanize of FHIT in suppressing the development of panereatic adenocarcinoma. The results and conclusions are as following. 1. Using the method of RT-PCR and Nested-PCR the study showed that the altered frequence of human pancreatic adneocarcinoma and their adjacent tissues were both high (66.7% and 60%) and were much higher than that of normal pancreas tissues (P<0. 01). The most common altered region of FHIT eDNA in the tissues analysed was no coding area exon 2 exon 4 and the first coding exon 5, the alter about FHIT is usually deleted one or several exon. The high altered frequence of FHIT is connected closely to the fragile region, the FRA3B locus. The FRA3B locus may have a special gene sequence suscep- tible to other agents that interfere with DNA replication, such as nicotine, caf- feine, alcohol, or other known carcinogens. The high frequence of altered FHIT in pancreatic adenocarcinoma adjacent tissues implicates that this tissues are easily oncology leading to the high relapse frequence after operation. So, FHIT gene plays an important role in the development of pancreatic adenocar- cinoma. FHIT gene was found lost totally in 1990 cell line. 2. The method of liposome transfection can get a high validity of transfec- tion. FHIT was tranfected to 1990 cell line in which the FHIT gene was lost totally. Integration and expression of exogenous FHIT gene were confirmed by RT-PCR and Western blotting. The growth of 1990 pFHIT was suppressed clearly and its tumorigericity in nude mice was reliminated or supressed also, all of which indicated that FHIT suppressed the growth and tumorigenicity of the panereatic adenocarcinoma cell line and supported FHIT is a tumor sup- pressor gene. So, a new approach is available to probe the mechanize and ther- apy protocols about pancreatic adenocarcinoma. 3. When the morphology of 1990 and 1990 pFHIT were evaluated, the apoptosis in 1990 pFHIT increased clearly. By the analysis of its DNA on a- garose gel for electrophoresis, the characteristic DNA ladder of 200 bp oc- curred. It could be spectulated that FHIT suppress the development of paner- catic adehocarcinoma by the path of apoptosis. The level of Ap3A in 1990 pFHIT decreased clearly than that of 1990. However, the level of Ap4A in 1990 pFHIT increased, the ratio of Ap4A to Ap3A changed more clearly. FHIT protein is a Ap3A hydrolase l but its suppression on tunror didn, t dependon its hydrosis active. Taken together, a role for FHIT as a proapototic factor...is in agreement with the structura1 and biochedrical studies indicating thatFHIT. Ap3A complex is the active FHIT form involved in cel1ular signalinglinking the induction of apoptosis in 1990 pFHIT celIs...
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