S100A7 Up-regulated The Expression Of CXCR4 Via EGFR/PI3K Pathway Induced By EGF

The incidence of breast cancer is rising year by year. And breast cancer is themost common malignant disease in world women by far. Metastasis of primary breast tumor cells through the blood or lymphatic system to distant organs is responsible for the majority of breast cancer deaths. Genomic characterization is beginning to define a molecular taxonomy for breast cancer; however, the molecular basis of invasion and metastasis remains poorly understood.S100 proteins family are a kind of the EF-hand type of calcium binding proteins in vertebrate,which are comprised of more than 20 members.They can participate in the phosphorylation of protein, the construction of cystoskeleton and transcription factor,as well as cell proliferation and differentiation. Psoriasin (S100A7) is a new member of S100 proteins family. S100 gene is often located in 1q21.2-q22 of the chromosome. S100A7 is initially found in the epidermis Keratinocyte of psoriasis,so it also called Psoriasin. S100A7has been shown to be expressed in various tumors,such as squamous cell carcinoma of the skin,lung cancer,cervix cancer and breast cancer and so on.Persistent expression of S100A7 occurs in some invasive cancer and is associated with poor prognostic factors.Chemokine receptor 4 (CXCR4) is a highly conservative member of the seven-transmembrane domain family of G-proteincoupled receptors.Various functions of CXCR4 have been shown in a great many studies. CXCR4 has been shown to be highly expressed in various tumors,and it plays an important role in tumor invasion and cell migration.We will primitively make a approach to check the relationship between S100A7 and CXCR4.We also check whether there is a regulatory relationship and the biological effects on the breast cancer cell.Materials and Methods1,We examined the expression of S100A7,CXCR4 and CD34 in normal breast and breast cancer with immunohistochemistry.we also examined the relationship among them.2,We also examined the CXCR4 expresion and protein expression level in the EGFR/PI3K pathway with Western blot in stable transfected breast cancer cell respectively S100A7-231 and vector-231.3,We check the influence of S100A7 on the cell functionwith the wound healing assay and transwell assay.4,Statistics with SPSS16.0 software and appling with logist-test and x2-test. P<0.05 means significance.Results一,We examined the expression of S100A7,CXCR4 and CD34 in normal breast and breast cancer with immunohistochemistry. we also examined the relationship among them.1,S100A7 almost do not express or lowly expressed in normal breast tissue. Only a weakly positive,the positive expression rate of S100A7 is 5%; CXCR4 do not express in normal breast tissue.2,S100A7 expresses in the cytoplasm and cell nucleus in breast intraductal carcinoma;CXCR4 expresses both in the cytoplasm and cell nucleus in breast intraductal carcinoma.3,The positive expression rate of S100A7 in ER(-) group is higher than ER (+) group. In ER(-) group,the positive expression rate of S100A7 in ER(-)PR(-)HER2(+) group is higher than ER(-)PR(-)HER2(-)group. The positive expression rate of S100A7 is respectively 62.2%and42.5%. In ER(+) group,the positive expression rate of S100A7 in ER(+)PR(+)HER2(+) group is higher than ER(+)PR(+)HER2(-)group. The positive expression rate of S100A7 is respectively 27.2%and15.6%%.S100A7 and HER2exist positive correlation.。4,The positive expression rate of CXCR4 in ER(-) group is slightly higher than ER (+) group. In ER(-) group,The positive expression rate of CXCR4 in ER(-)PR(-)HER2(+) group is higher than ER(-)PR(-)HER2(-)group. The positive expression rate of CXCR4 is respectively 79.2%and61.1%. In ER(+) group,the positive expression rate of CXCR4 in ER(+)PR(+)HER2(+) group is higher than ER(+)PR(+)HER2(-)group. The positive expression rate of CXCR4is respectively 78.2%and61%. CXCR4 and HER2 exist positive correlation.5,CXCR4andS100A7 exist positive correlation (r=0.433, p<0.05)6,CXCR4 and vessel density as well as S100A7 and vessel density exists positive correlation.二,We examined the protein expression level in the EGFR/PI3K pathway with Western blot in stable transfected breast cancer cell respectively S100A7-231and vector-231.1,S100A7 upregulates the expression of CXCR4.2,S100A7 activates EGFR/PI3K pathway induced by EGF:the expression of Phospho-EGFR and Phospho-IRS-1 are significantly higher than control.三,The influence on the breast cancer behavior.1,Wound healing assay shows that S100A7 can enhance the cell migration induced by EGF.2,Transwell assay shows that S100A7 can enhance the cell migration induced by EGF. Conclusions1,S100A7and CXCR4 almost do not express or lowly expressed in normal breast tissue.,while high expression in the intraductal carcinoma. CXCR4 andS100A7 exist positive correlation. CXCR4 and vessel density as well as S100A7vessel density exists positive correlation. CXCR4 and HER2 as well as S100A7and HER2 exists positive correlation in breast cancer.S100A7and CXCR4 play important roles in tumorigenesis and progression.in breast cancer.2,S100A7 upregulates the expression of CXCR4 induced by EGF and enhance the cell migration in breast cancer cell lines.