[The role of Smad4 and MAPK proteins in signal transduction pathway in non-small cell lung cancer].
OBJECTIVE
To investigate the expression of Smad4 in non-small cell lung cancer (NSCLC), its correlation with MAPK (mitogen activated protein kinase) and their clinical significance in NSCLC.


METHODS
Western blotting and RT-PCR were employed to test 42 resected lung cancers and normal lung tissues for the expression of Smad4. Imunohistochemistry was used to detect Smad4 and subtribes of MAPK in 71 paraffin samples.


RESULTS
The level of protein and mRNA expression of Smad4 in lung cancer tissues were 0.2092 +/- 0.1308 and 0.3986 +/- 0. 1982, respectively, lower than those in normal tissues (0.7852 +/- 0.4386 and 1.1206 +/- 0.6772, P < 0.05). The expression of p38, ERK1 and Smad4 was associated with TNM staging (P = 0.000, 0.000 and 0.005, respectively) and JNK1 with tumor location (P = 0.028) and staging (P = 0.000). There was a correlation between p38 and Smad4 (P = 0.000). The expression of Smad4 (P = 0.0001), p38 (P = 0.0000) and JNK1 (P = 0.0208), tumor differentiation (P = 0.0059) and staging (P = 0.0000) were significantly correlated with prognosis of NSCLC by univariate analysis. Smad4 (P = 0.019), p38 (P = 0.044), tumor differentiation (P = 0.003), and staging (P = 0.020) were correlated with prognosis tested by multivariable analysis. Taking p38 and Smad4 together, we found that the negative expression of p38 and positive expression of Smad4 were associated with a better prognosis of NSCLC (P = 0.000).


CONCLUSIONS
Smad4 could be of importance for the initiation and development of NSCLC. There is a significant correlation between main proteins of TGF-beta/smad4 and those of ras-MAPK signal transduction pathways. The expression of Smad4 is inhibited by p38. Smad4, as well as p38, tumor differentiation and staging can be used as prognostic factors of NSCLC.
Tong
Xiang-Dong
XD
Department of Thoracic Surgery, First Hospital, China Medical University, Shenyang 110001, China.
Liu
Hong-Xu
HX
Zhao
Hui-Ru
HR
Xu
Shi-Guang
SG
Li
Yu
Y
Han
Li-Bo
LB
Zhang
Lin
L
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases