[Expression of DPC4/Smad4, p21wafI, and p16 in human pancreatic cancer].
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Gu
Li-jun
LJ
Department of Pathology, PUMC Hospital, CAMS and PUMC, Beijing 100730, P. R. China.
Chen
Jie
J
Lu
Zhao-hui
ZH
Li
Li
L
Zhou
Wei-xun
WX
Luo
Yu-feng
YF
D015153:Blotting, Western; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D051901:Smad4 Protein; D015534:Trans-Activators / Q000032:analysis*
C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators