Comparative Expression of mRNA and Protein of DPC4 in Relation to Ubiquitin Expression in Various Pancreatic Duct Lesions of Human Pancreatic Cancer Tissue

Abstract

The expression of Dpc4 protein (pDpc4) is immunohistologically demonstrated in various cancer cells, but the expression of its mRNA has yet to be defined. The present study was designed to assess the correlation between pDpc4 expression and DPC4-mRNA expression, and between pDpc4 and DPC4-mRNA expression and ubiquitin (Ub) expression in human pancreatic cancer tissue. In 76 pancreatic duct lesions of 21 specimens of pancreatic cancer tissues, the expression of DPC4-mRNA was assessed by in situ hybridization (ISH), and the expression of pDpc4 and Ub was assessed by immunohistochemistry (IHC). The pancreatic duct lesions were classified according to the pancreatic intraepitherial neoplasia (PanIN) criteria. In normal duct or early neoplastic lesions (PanIN-1), both DPC4-mRNA and pDPC4 were widely expressed, and Ub expression was low. In borderline or low-grade malignancy lesions (PanIN-2 or PanIN-3), DPC4-mRNA was highly expressed, but pDpc4 expression was low, and Ub expression was high. On the other hand, in highgrade malignancy (ductal carcinoma) lesions, expression of both DPC4-mRNA and pDpc4 was low, but Ub was highly expressed. Although DPC4-mRNA was widely expressed, pDpc4 expression decreased, while Ub expression increased along with the progression of pancreatic malignancy. These results suggest that the decreased expression of pDpc4 may be caused by its degradation by highly expressed Ub. In addition, the decreased expression of DPC4-mRNA in high-grade malignancy suggests a homozygous deletion of the DPC4 gene.