[Expression and mutation of Fas-associated death domain (FADD) gene in non-small cell lung cancer].
OBJECTIVE
Abnormal expression of Fas-associated death domain (FADD) protein, an important adapter in cell apoptosis signal conduction, may closely relate with tumorigenesis. This study was to detect expression and mutation of FADD gene in non-small cell lung cancer (NSCLC), evaluate its effect on development of NSCLC, and explore the mechanism.


METHODS
Polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) was used to detect FADD gene mutation in 62 specimens of NSCLC tissues and 13 specimens of adjacent non-cancerous lung tissues. Immunohistochemistry was used to detect its protein expression. In situ hybridization (ISH) was used to detect FADD mRNA expression in 30 of the 62 specimens of NSCLC tissues. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick labeling (TUNEL) was used to detect apoptotic cells in NSCLC tissues.


RESULTS
Of the 62 specimens of NSCLC tissues, 4 cases of stage N2 showed FADD gene mutation. Positive rate of FADD protein in NSCLC tissues was 80.6% (50/62), its protein level positively correlated with differentiation of NSCLC (rs=0.411, P<0.01). Protein level of FADD in NSCLC tissue was significantly higher than that in non-cancerous tissue (P<0.05). Positive rate of FADD mRNA in NSCLC tissue was 80.0%, its concordant rate with positive rate of FADD protein was 88.6% (P>0.05). Apoptotic cells were observed in all specimens of NSCLC, apoptosis indexes of the 4 cases with FADD gene mutation were lower than the mean level, although they showed positive expression of FADD protein. Protein level of FADD was positively related with cell apoptosis of NSCLC (rs=0.599, P<0.001).


CONCLUSIONS
FADD gene mutation exists in NSCLC, its mutation and abnormal expression might play a crucial role in carcinogenesis of NSCLC. Protein level of FADD closely correlates with cell apoptosis of NSCLC.
Yang
Qin
Q
Department of Pathology, Medical College, Wuhan University, Wuhan, Hubei, 430071, P.R.China.
Zhu
Run-Qing
RQ
Fang
Zhong
Z
Xia
Dong
D
Diao
Lu-Ming
LM
Liu
Ming-Qiu
MQ
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D005091:Exons; D053200:Fas-Associated Death Domain Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D012333:RNA, Messenger