The Expression Of CARD9 In Breast Cancer Tissues And Its Functions On The Biological Behavior Of Breast Cancer Cells

Breast cancer is one of the most common malignant tumor in women,and tends to be more likely to recur or spread in younger women.Although,the progresses have been made in early diagnosis,surgical treatment,radiotherapy and targeted therapy for the treatment of breast cancer recently years,but the curative efficacy is less satisfactory.The efficiency of target therapy on breast cancer is also required to be improved.Therefore,the detection of the molecular mechanism on the pathologenesis of breast cancer and the new therapeutic targets are urgently things that need to be settled in breast cancer curing.CARD9 protein is an important adaptor protein,which binds to Bcl10,activates and regulates NF-?B and other signal pathway through the interaction between proteins,plays an important role in the occurrence and development of gastric B cell lymphoma,renal cell carcinoma,hepatitis C virus related hepatocellular carcinoma and colon cancer.However,its expression in breast cancer and its influence on the development of breast cancer has been rarely reported.The expressions of CARD9 mRNA and protein in breast cancer cell line T-47 D and MCF-7,normal breast cell line Hs578 Bst,breast cancer tissues and the adjacent normal tissues were detected by real-time fluorescent quantitative PCR and Western blotting,respectively.The correlation between CARD9 expression and clinicopathological features was analyzed.WST-1 assay,plate clone formation assay,flow cytometry and scarification assay were conducted to test the proliferation,cell apoptosis,cell cycle,invasion and metastasis of breast cancer cells respectively after enhancing the expression level of CARD9 via transient transfection.Finally,we analysed the correlation between CARD9 expression and activation of NF-?B signaling pathway,and explored the possible mechanismconcerned.The results showed that the expressions of CARD9 mRNA(P < 0.01)and protein(P = 0.012)in breast cancer tissues were higher than those in the adjacent normal tissues.The expression of CARD9 mRNA in breast cancer T-47 D cells(P = 0.021)and MCF-7 cells(P = 0.014)was higher than that in normal breast Hs578 Bst cells.The expressions of CARD9 mRNA and protein in breast cancer ZR-75-1 cells were higher than those in normal breast Hs578 Bst cells(P = 0.003 and P = 0.01).Expression of CARD9 protein was positively correlated with the tumor size and ER(both P < 0.015).Enhancing the expression of CARD9 could promote the proliferation of breast cancer cells(P < 0.05),while had no effect on cell apoptosis,cell cycle,Invasion and metastasis of breast cancer cells.The expressions of P50(P < 0.05),P65(P = 0.098),p-IKK?(P < 0.01)in breast cancer tissues were higher than those in the adjacent normal tissues.The mRNAs expressions of p50(r = 0.622,P < 0.01),p65(r = 0.392,P = 0.005),IL-1?(r = 0.685,P < 0.01),IL-12(r = 0.556,P < 0.01)were positive correlated with the expression of CARD9 mRNA.The results of this study revealed the expression of CARD9 in breast cancer and its relationship with the clinicopathological features of breast cancer.Meanwhile,it was found that CRAD9 could promote the proliferation of breast cancer cells by activating the NF-?B signaling pathway.In this way CARD9 participate in the development of breast cancer.These findings contribute to a better understanding of the potential value of CRAD9 in the development and treatment of breast cancer,and make CARD9 a new key risk indicator for breast cancer.It can provide a theoretical evidence for CARD9 to become a new therapeutic target for breast cancer and provide new ideas for the diagnosis and treatment of breast cancer.