14-3-3 ζ And Metastasis Of Lung Cancer: An Experimental Investigation

Suppression subtractive hybridization (SSH) accompanied by DNA array is an effective method to isolate differential phenotype associated genes. Using this technique, We isolated 41 differentially expressed sequences associated with poorly metastatic phenotype. In current study, we made bioinformatical analysis on sequence 64 and found it is highly homologous to 14-3-3 ζ . As there is no report on the relation between 14-3-3 ζ and metastasis of lung cancer, we will discuss the probable function of 14-3-3 ζ in metastasis of lung cancer here.We examined the expression of 14-3-3 ζ between PLA801C and PLA801D by RT-PCR, Western blot and immunocytochemical staining. The results revealed that 14-3-3 ζ expressed much more highly in PLA801C than in PLA801D. Then the sense and antisense expression vector were constructed and transfected into PLA801C and PLA801D. Examination of the expression of 14-3-3 ζ in stable transfected cell lines showed that transfection of sense expression vector enhanced its expression, while antisense expression vector reduced its expression.With the stable transfected cell lines, we studied cell's ability of proliferation,adhesion and migration and found that overexpression of 14-3-3 ζ could reduce the abilityof proliferation and migration, but enhance the ability of adhesion; while inactivation of14-3-3 ζ led to the opposite results. These results suggested that overexpression of 14-3-3ζ may inhibit the metastasis of lung cancer cells.RNAi technology was also employed to study the relation between 14-3-3 ζ and metastasis. Cells transfected with RNAi vector showed much lower 14-3-3 ζ expression and ability of adhesion, but much higher ability of migration and invasion.Immunohistochemical staining of primary and metastatic carcinoma from 20 lung cancer patients showed that in 15 patients, 14-3-3 ζ expressed more highly in primary than in metastatic carcinoma.In summary, 14-3-3 ζ may have a high correlation with tumor metastasis, overexpression of 14-3-3 ζ may inhibit metastasis while inactivation of 14-3-3 ζ may facilitate metastasis. The mechanism remains to be studied. 14-3-3 ζ can be an effective marker for lung cancer diagnosis.