The Expression And Function Of Protein Kinase D2(PKD2) In Non Small-cell Lung Cancer

Background:Widely expressed as PKD were, the function of it is still unknown. Present study proves that PKD is mainly regulated by the G protein coupled receptor (GPCR). When extracellular signal stimulates GPCR, the second messager DAG then active. DAG active PKD through PKC signal and direct effects. Phosphorylated PKD transfer from membrane to the nucleus, involved in mitosis cascade signal and act with beta-catenin, HDAC, ERK and NF-kappa B and JNK signaling molecules. Certain hormones or cytokines such as gastrin, vasopressin through active PKD, thus influence the proliferation, differentiation and apoptosis of tumor cells.PKD in regulating cell proliferation, migration and other biological behaviour has played a very important role. PKD by combining JNK and ERK1/2, regulating there active status, and thus stimulate cell proliferation; PKD can also raise, by promoting integrin affect tumor cell invasion; And, PKD also involved in the regulation of stress and disease state.PKD is divided into three subtypes, PKD1,PKD2and PKD3. Different subtypes of PKD plays different role in various malignant tumor. PKD1subtype is one of the most intensively studied, the study found that PKD1in breast cancer, prostate cancer and other tumors can inhibit tumor proliferation, migration, and participate in maintaining epithelial phenotype. Part of the study think PKD2and PKD3can promote cell malignant transformation. PKD2and PKD1have similar molecule structure but their downstream pathway is not exactly the same. In various malignant tumor, PKD1and PKD2express or absence can cause different effect.Object: PKD2and malignant degree is related with the incidence of lung cancer, PKD2how to affect the cell biological characteristics, through which pathways play a role, and PKD2as a possible new targets for lung cancer treatment.Methods:1. We get lung cancer tumor tissue (T) and normal tissues (N) from33cases of patients, and make a RT-PCR. With the result by paired T test to confirm the expression of PKD2whether there is a difference in the tumor and normal tissue.2. To analyze the clinical data of33patients, can verify PKD2as prognostic factors, and the expression of PKD2and is associated with the degree of malignant tumor.3. Known PKD2in some tumor cell lines (e.g. high expression in A549), confirmed PKD2expression in normal and tumor cell lines.4. Using the high expression of PKD2cell line (A549) validation PKD2biological effect of cell.5. Using western blot test the transfection group and the normal group to identify the key enzyme may associated with PKD2.Results:1. PKD2expression in normal tissue and tumor tissue has no obvious difference, and there has no obvious correlation between PKD2expression and the clinical pathological parameters, at the same time, the expression of PKD2has no obvious correlation with the patient survival.2. The cell experiment confirmed that PKD2transfection knockout can significantly inhibit cell activity and proliferation.3. Western blot confirmed PKD2can affect p-ERK, p-S6K1, p-S6, p-Akt activation.Conclusion:1. PKD2expressed in tumor and normal tissue has no obvious difference, and the expression of PKD2has no obvious contact with survival time.2. knockout PKD2can induce cell proliferation decrease.3.PKD2may mediate the phosphorylation of P70, ERK, AKT and S6thus influence the proliferation of tumor cells.4. PKD2may play a role in cancer development and promoting tumor.Meaning: PKD2promotes the development of tumor, and PKD2expression in the organization has a certain specificity, can consider to use it as a molecular targets for drug development.