β-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: Relationships with carcinogenesis and metastasis

AIM: To investigate whether abnormal expression of β catenin in conjunction with overexpression of cyclinD1, cmyc and matrix metalloproteinase-7 (MMP-7) correlated with the carcinogenesis, metastasis and prognosis of pancreatic cancer, and to analyze the relationship of βcatenin expression with cyclinD1, c-myc and MMP-7 expression.METHODS: Using immunohistochemistry, we examined the expression of β-catenin, cyclinD1, c-myc and MMP-7 in 47 pancreatic adenocarcinoma tissues, 12 pancreaticintraepithelial neoplasia (PanIN) and 10 normal pancreases, respectively. Proliferation cell nuclear antigen was also tested as the index of proliferative activity of pancreatic cancer cells.RESULTS: In 10 cases of normal pancreatic tissues, epithelial cells showed equally strong membranous expression of β-catenin protein at the cell-cell boundaries, but the expression of cyclinD1, c-myc and MMP-7 was negative. The expression of β-catenin, cyclinD1, c-myc and MMP-7 in PanIN and pancreatic adenocarcinoma tissues had no significant difference 6/12 and 32/47 (68.1%), 6/12 and 35/47 (74.5%), 5/12 and 33/47 (70.2%), 7/12and 30/47 (63.8%), respectively]. The abnormal expression of β-catenin was significantly correlated to metastasis and one-year survival rate of pancreatic cancer, but had no relation with size, differentiation and cell proliferation. The expression of cyclinD1 was correlated with cell proliferation and extent of differentiation, but not with size, metastasis and one-year survival rate of the pancreatic cancer. The expression of c-myc was not correlated withsize, extent of differentiation, metastasis and 1-year survival rate, but closely with cell proliferation of pancreatic cancer. The overexpression of MMP-7 was significantly associated with metastasis and 1-year survival rate ofpancreatic cancer, but not with size, extent of differentiation and cell proliferation. There was a highly significant positive association between abnormal expression of β-cateninand overexpression of cyclinD1, c-myc and MMP-7 not only in PanIN (r = 1.000, 0.845, 0.845), but also in pancreatic cancer (r = 0.437, 0.452, 0.435).CONCLUSION: The abnormal expression of β-catenin plays a key role in the carcinogenesis and progression of human pancreatic carcinoma by up-regulaling the expression of cyclinD1, c-myc and MMP-7, resulting in the degradation of extracellular matrix and uncontrolled cell proliferation and differentiation. β-catenin abnormal expression and MMP-7 overexpression may be considered as two useful markers for determining metastasis and prognosis of human pancreatic cancer.