Experimental Study On TLR4/MyD88 Signaling Pathway And Invasiveness Of Breast Cancer

Purpose The impact of TLR4/My D88(Toll-like receptors 4/ myeloid differentiation factor 88) on the invasion and metastasis of malignant tumor cells, which include ovarian cancer, rectal cancer and prostate cancer, has been widely reported. The purpose of this research is to study the expression and significances of TLR4/My D88 in breast cancer cells and provide a new strategy for breast cancer treatment.Methods(1) TLR4, My D88 and HMGB1 m RNA expression levels were detected in human high invasive breast cancer cells MDA-MB-231 and poor invasive breast cancer cells MCF-7 by reverse transcription-polymerase chain reaction(RT-PCR). TLR4, My D88 and HMGB1 protein expression levels were detected by Western-Blot and immunofluorescence methods.(2) One hundred cases of breast cancer tissue and para-carcinoma tissue were selected randomly from specimen repository in our department using the table of random digits. TLR4, My D88 and HMGB1 protein expression levels of these tissues were detected by immunohistochemical method.Result(1) Human breast cancer cells MDA-MB-231 and MCF-7 expressed TLR4, My D88 and HMGB1 at both m RNA and protein levels. The m RNA expression of TLR4 and My D88 in MDA-MB-231 cells was obviously higher than in MCF-7 cells respectively, and the expression in MDA-MB-231 cells was(10.43±4) and(2.09±1.5) times as much as in MCF-7 cells(P<0.01). The protein expression of TLR4 and My D88 in MDA-MB-231 cells was obviously higher than in MCF-7 cells respectively, and the expression in MDA-MB-231 cells was(9.18±3.2) and(2.52±1.0) times as much as in MCF-7 cells(P<0.01). The m RNA and protein expression of HMGB1 in both breast cancer cell lines were comparable, with no statistical difference(P>0.05).(2) TLR4, My D88 and HMGB1 protein expression levels of breast cancer tissue and para-carcinoma tissue were 46% vs 20%, 41% vs 25% and 76% vs 20%, with statistical differences(P<0.001 for all). TLR4, My D88 and HMGB1 protein expression levels were positively correlated to axillary lymph nodes metastasis and histological grade(P<0.05),but were not correlated to age,family history of malignancy and diameter of breast cancer(P>0.05).Conclusion The invasive level and the expression level of TLR4/My D88 in breast cancer cells were consistent. TLR4/My D88 expression levels were positively correlated to clinical and pathological features, including axillary lymph nodes metastasis and histological grade. The expressions of TLR4/My D88 may be used as predictive molecular marks in evaluating outcome and guiding therapeutic strategy of breast cancer.