Induction and expression of cyclin D3 in human pancreatic cancer

Purpose: Cyclins play a key role in the control and regulation of the cell cycle. The;role of cyclins in the pathogenesis of pancreatic cancer is larg ely unknown. Methods: Using Northern blot analysis, polymerase chain reacti on (PCR) and immunohistochemistry, we examined the expression of cyclins D1 , D2, and D3 in human pancreatic cancer and studied the induction of these cyclins by growth factors in pancreatic cancer cell lines. Results: We now report that cyclin D1 and D3 mRNAs are expressed in human pancreatic cancer cell lines, and that the expression of cyclin D3 is enhanced in pancreatic cancer cells by amphiregulin, a member of the epidermal growth factor fami ly. Cyclins D1 and D3 are also expressed in normal and malignant pancreatic tissues. However, while the normal pancreas and pancreatic cancers express cyclin D2 as determined by reverse-transcriptase PCR, we could not detect cyclin D2 mRNA by either Northern blot analysis or reverse transcriptase PC R in the two pancreatic cancer cell lines. Immunohistochemical analysis rev ealed the expression of cyclin D3 in pancreatic cancer cells. Conclusions: These findings suggest that D-type cyclins are differentially expressed in pancreatic cancer and that the aberrant activation of the EGF receptor in h uman pancreatic cancer by amphiregulin may lead to the progression of the c ell cycle via induction of cyclin D3 expression, thus contributing to the g rowth advantage of these transformed cells.