Gu Li-jun, Chen Jie, Lu Zhao-hui, Li Li, Zhou Wei-xun, Luo Yu-feng
Department of Pathology, PUMC Hospital, CAMS and PUMC, Beijing 100730, P. R. China.
Ai Zheng. 2002 Feb;21(2):132-7.
BACKGROUND & OBJECTIVE: DPC4/Smad4 inactivation was detected in almost half of the pancreatic carcinomas result in the loss of inhibition of the tumor cell proliferation. p21wafI is the downstream target gene of Smad4 while DPC4 and p16 may synergistically play a role in the development of pancreatic carcinoma. By studying the expressions of DPC4/Smad4, p21wafI, and p16. This study was designed to explore the mutual relationship among them and the possible mechanism in human pancreatic carcinoma.
Immunohistochemistry was used to detect the expression of Smad4, p21wafI, and p16 in fifty-six samples of paraffin embedded human pancreatic cancer tissue, and in situ hybridization, immunohistochemistry, Western blotting technique were used to detect the expression of DPC4/Smad4 in five human pancreatic adenocarcinoma cell lines.
The positive rate of Smad4, p21wafI, and p16 in paraffin embedded human pancreatic cancer tissue was 58.93%, 48.21%, and 42.86%, respectively, whereas the positive rate of these proteins in matched normal tissue was 89.29%, 87.5%, and 76.79% respectively. Three out of five pancreatic adenocarcinoma cell lines (P3, P4, and P7) were positive for DPC4/Smad4 with in situ hybridization, immunohistochemistry and Western blotting, while the other two lines were all negative. There is statistically significant difference between cancer and normal tissue (P < 0.05). In pancreatic adenocarcinomas, the expression of Smad4 was related to that of p21wafI (P < 0.05), and so was the expression of Smad4 to that of p16 (P < 0.05). But no correlation was found between p21wafI and p16 (P > 0.05).
The expression of Smad4, p21wafI, and p16 significantly decreased in pancreatic cancer compared with normal tissue. The decreased expression of the proteins may play an important role in the development of pancreatic cancer.
在近半数胰腺癌中检测到DPC4/Smad4失活，导致肿瘤细胞增殖抑制作用丧失。p21wafI是Smad4的下游靶基因，而DPC4和p16可能在胰腺癌的发生发展中协同发挥作用。通过研究DPC4/Smad4、p21wafI和p16的表达情况，本研究旨在探讨它们之间的相互关系以及在人胰腺癌中的可能机制。
采用免疫组织化学法检测56例石蜡包埋的人胰腺癌组织中Smad4、p21wafI和p16的表达，采用原位杂交、免疫组织化学和蛋白质印迹技术检测5种人胰腺腺癌细胞系中DPC4/Smad4的表达。
石蜡包埋的人胰腺癌组织中Smad4、p21wafI和p16的阳性率分别为58.93%、48.21%和42.86%，而在配对的正常组织中这些蛋白的阳性率分别为89.29%、87.5%和76.79%。5种胰腺腺癌细胞系中有3种（P3、P4和P7）经原位杂交、免疫组织化学和蛋白质印迹检测DPC4/Smad4呈阳性，而另外2种细胞系均为阴性。癌组织与正常组织之间差异有统计学意义（P<0.05）。在胰腺腺癌中，Smad4的表达与p21wafI的表达相关（P<0.05），Smad4的表达与p16的表达也相关（P<0.05）。但p21wafI与p16之间未发现相关性（P>0.05）。
与正常组织相比，胰腺癌中Smad4、p21wafI和p16的表达明显降低。这些蛋白表达的降低可能在胰腺癌的发生发展中起重要作用。
