Potential Role Of Neutrophil Elastase In The Development Of Lung Cancer

Lung cancer is a malignant tumor commonly seen in human being. Its incidence lies on the top of all malignant tumors, being the main cause of death due to malignancy in many countries. As a member of the trypsin superfamily and a powerful serine protease, nertrophil elastase (NE) is capable of degrading most proteins of the extracellular matrix, and various proteins of the coagulation and complement cascades. The crucial role of NE could be a double-edged sword, since it takes part in host defense, tissue turnover, and in abnormal self-destruction as well. NE protein has been studied in regard to the aggressiveness of the tumor. It was reported that NE protein was secreted from NSCLC cell lines, and the locally produced of NE was involved not only in the invasion of the tumor itself but also associated with a poor prognosis. To investigate whether NE is related to the development of small cell lung cancer, we, using molecular biology and immunology method, detected NE expression and NE promoter repetitive sequence in the tissues small cell lung cancer. The promoter activity of wild type and mutant NE promoter was compared through inserting both promoters into pGL3-Basic to construct luciferase expression vector.The results showed that 1. The NE level in tissue extract of T3 and T4 lung cancer was much morehigher than those of T1 and T2, and the same for stage III A and IIIB lung cancer which had high NE expression compared with stage I and II lungcancer. So we conclude that the level of NE expression in NSCL is closely related to the TNM staging and localization or size of the primary tumor.2. It was found that NE expression in SCLC was related to the stage of the disease, since we had detected high level NE expression in the tissues of expansive stage of SCLC but not limited stage.3. An outstanding finding of this study was that there were 1 case of NSCLC whose NE promoter gene sequence had transversion mutant from A to C occurred in the 48th base of region 3 and 6; and 2 cases of SCLC whose NE promoter gene sequence had frame shift mutant from GAC to GAAC occurred in the 3th base of region 6.4. Luciferase expressed in K562 cells transfected with mutant NE promoter luciferase expression vector was considerately higher than those transfected with wild type NE promoter luciferase expression vector.CONCLUSION:NE is over expressed in lung cancer and the level of its expression is closely related with the stage of the tumor. NE promoter gene replacement mutant and frame shift mutant in the region 3 and 6 may be the cause of a higher expression of NE enzyme, which promoted the invasion of lung cancer cell within the matrix. Our findings indicated that NE may play an important role in the development of lung cancer.