Ebert M P, Hernberg S, Fei G, Sokolowski A, Schulz H U, Lippert H, Malfertheiner P
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University of Magdeburg, Germany.
J Cancer Res Clin Oncol. 2001 Jul;127(7):449-54. doi: 10.1007/s004320100235.
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 largely unknown.
Using Northern blot analysis, polymerase chain reaction (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.
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 family. 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 PCR in the two pancreatic cancer cell lines. Immunohistochemical analysis revealed the expression of cyclin D3 in pancreatic cancer cells.
These findings suggest that D-type cyclins are differentially expressed in pancreatic cancer and that the aberrant activation of the EGF receptor in human pancreatic cancer by amphiregulin may lead to the progression of the cell cycle via induction of cyclin D3 expression, thus contributing to the growth advantage of these transformed cells.
细胞周期蛋白在细胞周期的控制和调节中起关键作用。细胞周期蛋白在胰腺癌发病机制中的作用尚不清楚。
我们采用Northern印迹分析、聚合酶链反应（PCR）和免疫组织化学方法，检测了细胞周期蛋白D1、D2和D3在人胰腺癌中的表达，并研究了这些细胞周期蛋白在胰腺癌细胞系中受生长因子的诱导情况。
我们现在报告，细胞周期蛋白D1和D3的mRNA在人胰腺癌细胞系中表达，并且作为表皮生长因子家族成员之一的双调蛋白可增强胰腺癌细胞中细胞周期蛋白D3的表达。细胞周期蛋白D1和D3也在正常和恶性胰腺组织中表达。然而，虽然通过逆转录酶PCR检测发现正常胰腺和胰腺癌均表达细胞周期蛋白D2，但我们通过Northern印迹分析或逆转录酶PCR在两种胰腺癌细胞系中均未检测到细胞周期蛋白D2的mRNA。免疫组织化学分析显示胰腺癌细胞中存在细胞周期蛋白D3的表达。
这些发现表明D型细胞周期蛋白在胰腺癌中存在差异表达，并且双调蛋白对人胰腺癌中表皮生长因子受体的异常激活可能通过诱导细胞周期蛋白D3的表达导致细胞周期进程，从而促成这些转化细胞的生长优势。
