Expression of Ezrin, HGF, C-met in pancreatic cancer and non-cancerous pancreatic tissues of rats.
BACKGROUND
Recent studies have confirmed that the expression of Ezrin, hepatocyte growth factor (HGF) and its receptor (C-met) is related to the genesis, progress, invasion and metastasis of some malignant tumors. Researches have also found that the biological function of Ezrin is closely related to HGF/C-met in malignant tumors. However, there is no report on the expression levels of Ezrin, HGF and C-met in rat pancreatic cancer induced by dimethylbenzanthracene (DMBA). This study aimed to detect the expression of Ezrin, HGF and C-met in rat pancreatic cancer and non-cancerous pancreatic tissues, and assess its effect in cancer induction by DMBA.


METHODS
Ninety Sprague-Dawley rats were divided into 3 groups randomly: 40 in a pancreatic cancer model group (group A), 40 in a trichostatin A (TSA) intervention group (group B), and 10 in a control group (group C). DMBA was directly implanted into the parenchyma of rat pancreas in group A+group B. The rats of group B were treated with 1 ml of TSA saline solution (1 μg/ml) via intraperitoneal injection weekly. The carcinogenesis of rats executed within 3-5 months in groups A and B was observed by macrograph and microscopy. Meanwhile, the rats in group C were executed within 5 months. The EnVisionTM immunohistochemistry for detecting the expression levels of Ezrin, HGF and C-met was used in paraffin-embedded sections of the pancreatic specimens.


RESULTS
The incidence of pancreatic cancer in group A was 48.6% and in group B 33.3%. The maximal diameter of tumor mass was significantly larger in group A than that in group B (P<0.05). No pathological changes were observed in the pancreas of group C and other main organs of groups A and B. The positive rates of Ezrin, HGF and C-met were significantly higher in ductal adenocarcinoma than in non-cancerous pancreatic tissues of groups A and B (P<0.01). The positive rates of Ezrin, HGF and C-met were significantly higher in ductal adenocarcinoma of group A than those in non-cancerous pancreatic tissues of group A (P<0.05), but there was no significant difference in group B (P>0.05). The positive rates of Ezrin, HGF and C-met in non-cancerous pancreatic tissues proved mild to severe atypical hyperplasia of the ductal epithelia. The pancreas of group C and 2 cases of fibrosarcoma showed the negative expression of Ezrin, HGF and C-met. There was a trend of consistency in the expression of Ezrin, HGF and C-met in ductal adenocarcinoma (P<0.05 or P<0.01).


CONCLUSIONS
DMBA directly implanted into the parenchyma of the pancreas can produce a model of pancreatic cancer with a high incidence in a short time. TSA might inhibit the carcinogenesis and growth of pancreatic cancer, and its effects may be related to the inhibition of the expression of Ezrin, HGF and C-met during the process. Ezrin, HGF and C-met may have positive effects on the carcinogenesis of rat pancreas.
Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Xing-Guo
XG
Tan
Zhu-Lin
ZL
Yang
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D021441:Carcinoma, Pancreatic Ductal / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005354:Fibrosarcoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D007150:Immunohistochemistry; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099149:Ezrin
D015127:9,10-Dimethyl-1,2-benzanthracene; D002273:Carcinogens; D003598:Cytoskeletal Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D000099149:Ezrin