[Expression of apoptosis and proliferation related genes in carcinogenesis of lung squamous cell carcinoma in rats].
OBJECTIVE
The activation of caspase-3 protein, located the downstream of apoptosis, is the key of cell apoptosis signal conduction. Caspase-3 is the most important performer in accelerating apoptosis in the caspase family. Much progress has been achieved in the study of caspase-3 and human non-small cell lung cancer. This study was designed to investigate the effect of cellular proliferation and apoptosis related genes caspase-3 and proliferating cell nuclear antigen (PCNA), and to seek whether they could be chosen as molecular biology markers for lung cancer.


METHODS
3-Methylcholanthrene (MCA) and diethyinitrosamine (DEN) were used to induce lung squamous cell carcinoma by intra-left lobar-bronchial instillation in 50 Wistar rats. The other 10 rats instilled with iodized oil were regarded as control group. The expression of caspase-3 and PCNA were evaluated by SP immunohistochemistry during carcinogenesis. TUNEL(TDT-mediated dUTP nick end labeling) method was used to examine apoptotic cells.


RESULTS
For the rat bronchial epithelium cells in control group, precancerous lesions, and lung squamous cell carcinoma, positive coefficient values of caspase-3 protein were 3.10+/-0.99, 2.25+/-1.13, and 1.38+/-0.95 on average, respectively; the means of PCNA-labeling index (PCNA-LI)were 14.10+/-5.02, 28.13+/-8.72, and 41.88+/-14.24, respectively; the means of apoptotic index(AI) were 0.60+/-0.52, 2.06+/-0.85, and 2.26+/-1.14, respectively.Significant differences in caspase-3 protein expression were observed between bronchial epithelium in control group and lung squamous cell carcinoma (P< 0.01). Caspase-3 expression was showed stronger in precancerous lesions than that in lung cancer (P< 0.05). Low proliferation index and low AI were detected in rat bronchial epithelium region in control group,which were significant differences in precancerous lesions and lung cancer, respectively (P< 0.01). In 34 rats with lung squamous cell carcinoma, there was negative relationship between caspase-3 and PCNA-LI (r=-0.7306, P< 0.01), so did it in AI and PCNA-LI(r=-0.8127,P< 0.01), but there was no relationship between caspase-3 expression and AI(P >0.05).


CONCLUSIONS
Loss of caspase-3 expression may be associated with the development of lung squamous cell carcinoma in Wistar rats, but it is not associated with AI. PCNA-LI is an important marker for malignant progression of lung cancer.
Wang
Jun
J
Department of Pathology, Medical College, Wuhan University,Wuhan, Hubei, PR China.
Chen
Hong-Lei
HL
Zhu
Run-Qing
RQ
Diao
Lu-Ming
LM
Jang
Man
M
Yang
Fei
F
Liu
Ming-Qiu
MQ
D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D005260:Female; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018809:Proliferating Cell Nuclear Antigen; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases