Expression And Application Of Follistatin In Human Lung Cancer

Follistatin is a single polypeptide chain,which was isolated fromovarian follicular fluid and directly inhibit the secretion of FSH fromanterior pituitary cells. Follistatin has a widely histologicaldistribution, follistatin mRNA with highest expression in adult ovary,pituitary,kidney,in fetal heart and liver. The character of FSexpression indicates that it may have a different function on differentkind of cells. FS can specifically binds activin, directly inhibitactivin`s biological activity and take part in many adjusting ofphysical function. Mouse gene knock indicate: FS plays importmentrole from former of embory to maturity of organism, FS often coexistand express with activin to make a balance system for maintainingnormal growth of organization and organ. One is over expression oranother decrease will result in imbalance of FS-ACT system, and withphysiological defect and the course of pathology of some organizationand organ. In the present study, FS was involved in forming of hepaticfibrosis, lung fibrosis, renal injure, injure of skin, injure of brain,atherosclerosis, PCOS, disease of reproduction amd gonal.ACTH can be examined in the extractive of organization of lungcancer (small cell lung cancer, squamocarcinima, adeno and squamocancer, adenocarcinoma). Cytoplasm of small cell lung cancercontains neuron secretive granulae, can secrete ACTH,5-HT,kinin,histamine, at the same time, 5-HT, kinin and histamine can adjust andraise ACTH level in the serum.Cultivated cell lines of small cell lungcancer can secrete ACTH. Activin A inhibin ACTH secretion fromsmall cell lung cancer, if FS was joined into the fluid, the action willdisappered completely. All these indicated that FS-ACT havecorrelation with lung cancer, especially small cell lung cancer.1. Research objectiveTo investigate FS`s expression and application in lung cancer,possible origin of serum FS about patient with cancer, secretivepathway, influential factor and signal trsnsduction mechanism.2. Research methods(1) Circular FSmRNA of different patients such as-lung tumor(small cell lung cancer, squamocarcinima, adeno and squamo cancer,adenocarcinoma), ovarian cancer, hepatic carcinoma, gastriccarcinoma, cancer of breast, renal carcinoma and non-tumor diseasefor example diabetes, hyperthyroidism and the normal health groupwas tested by using fluorescent-quantitative RT-PCR.(2) Lung tumor (small cell lung cancer, squamocarcinima, adenoand squamo cancer, adenocarcinoma and lung benign disease wereanazyled by immunohistochemistry.(3) To observe the origin of FS in tumor patients, we selectedorganization of tumor that obtained from operative patients with highFS, separated tumor cell and cultivate it, FS level was examined incultivated tumor cell by ELISA.(4) Using activator TPA and Forskolin that general trsnsductionpathway of signal to stimulate cultivated tumor cell.3. Research results(1) Circular FS mRNA of lung cancer and ovarian cancer is greatlyhigher than that of the normal health group, Difference is significantlyby statistics. P<0.01 and P<0.05, other cancer have no obviouschange.in lung cancer group, Circular FS mRNA of small cell lungcancer is the highest,then the adeno and squamo cancer,squamocarcinima, adenocarcinoma.(2) Immunohistochemistry staining showed that positive granulaewas distributed in cytoplasm. FS was not expressed in cytoplasm ofnormal cylindrical epithelial cell, differential tumor indicated differentFS level, positive rate is in turn: adenocarcinoma>adeno and squamocancer> squamocarcinima>small cell lung cancer>lung benign disease.(3) Serum FS level of patients with tumor is probable directlysecreted by tumor cell. Secretion of FS in tumor cells has character ofserum dose-dependent, high serum can increase FS level.(4) TPA, activator of PKC, can increase secretion of FS and hasdose-dependent. Forskolin, activator of PKA, has no obviousinfluence with FS.4. Research conclusionCircular FS mRNA levels of parients with lung cancer and ovarycancer are high expression, and difference significantly compared withnormal control group. In lung cancer, FS mRNA levels of small celllung cancer is the highest. Circular FS of patients with cancer candirectly derive from secretion of tumor cell. Secretion of FS by tumorcell has related to signaling transduction pathway of PKC.Immunohistochemistry staining showed that distribution andexpression level of FS is different in the diverse tumor, circular FSmRNA levels of patients is also markedly changing in the varioustumor. These findings suggest that FS expression of tumor cells andCircular FS mRNA levels have important diagnosis volue anddetermine types of tumor in the different lung cancer. Yet, It deservesfurther to study that abnormal high levels of FS mRNA was cause oftumorgenesis or the result of tumorgenesis.