Study Of Molecular Mechanism Of β2-microglobulin Regulation In HER-2(+) Breast Cancer

β2-microglobulin(β2-M)is a non-glycosylated protein with a molecular weight of 12-kDa synthesized in all nucleated cells and an important structural protein.Dissociativing β2-M demonstrated relatively low levels in human serum,urine,and other body fluids in normal physiological conditions,but serum β2-M content in some malignant patients greatly increasing,β2-M as a growth stimulating factor and cell signaling molecules in a variety of solid tumors to regulate cancer cell survival,proliferation,invasion,metastasis and angiogenesis.β2-M or its participation in the regulation of signaling pathways hope to become a promising new target for cancer treatment.Because breast cancer has different molecular typing,and different molecular types of breast cancer patients have different therapeutic effects and prognosis,so β2-M may be through different molecular mechanisms or signal pathway to participate in tumor regulation.We make β2-M gene overexpression and silence by transfecting the β2-M over-expression vector and small interfering RNA in human breast cancer cell lines BT474 and MDA-MB-453.Respectively,analysis of the predicted downstream gene changes of β2-M regulation by Real-time PCR and Western blotting.Then,using immunohistochemistry to verify β2-M may participate in regulation of signaling pathway between breast cancer tissues and adjacent tissues.The result shows that 1)β2-M regulated signal pathway is different in two molecular types of breast cancer.2)In ER+,PR+ breast cancer cell,β2-M involved in β2-M/HIF-1α/VEGF/P-SGK/Bcl-2 signaling pathway to join regulation,and supress HER-2 by β2-M/HER-2/P-ERK1/2/Bcl-2 signal pathway to participate in negative control,β2-M do not regulate by β2-M/HIF-1α/VEGF/P-ERK1/2/Bcl-2,β2-M/P-CREB/VEGF/P-SGK/Bcl-2 and β2-M/P-CREB/VEGF/P-ERK1/2/Bcl-2 signal pathway,there is a positive correlation in β2-M/HIF-1α,HIF-1α/VEGF,VEGF/P-SGK,P-SGK/Bcl-2.3)In ER-,PR-breast cancer cell,β2-M involved in β2-M/HIF-1α/VEGF/P-ERK1/2/Bcl-2 andβ2-M/HIF-1α/VEGF/P-SGK/Bcl-2 signaling pathway to join regulation,and β2-M do not regulate by β2-M/P-CREB/VEGF/P-SGK/Bcl-2,β2-M/P-CREB/VEGF/P-ERK1/2/Bcl-2 andβ2-M/HER-2/P-ERK1/2/Bcl-2 signal pathway,there is a positive correlation in β2-M/HIF-1α,HIF-1α/VEGF,VEGF/P-ERK1/2,VEGF/P-SGK,P-ERK1/2/Bcl-2,P-SGK/Bcl-2.4)In ER+,PR+,HER-2+molecular type,when upregulation of β2-M,HIF-1α,VEGF,Bcl-2 and P-SGR upregulation,P-ERK1/2 and P-CREB is not significantly change.In ER-,PR-,HER-2+ molecular type,when upregulation of β2-M,HIF-1α,VEGF,Bcl-2,P-ERK1/2 and P-SGR upregulation,P-CREB is not significantly change.In summary,in ER+,PR+,HER-2+ molecular type,β2-M regulate by β2-M/HIF-1α/VEGF/P-SGK/Bcl-2 and β2-M/HER-2/P-ERK1/2/Bcl-2 signaling pathway,In ER-,PR-,HER-2+molecular type,β2-M regulate by β2-M/HIF-1α/VEGF/P-ERK1/2/Bcl-2 and β2-M/HIF-1α/VEGF/P-SGK/Bcl-2 signaling pathway.This result will help us to understand further the β2-M regulation in HER(+)breast cancer molecular mechanism,illustrating the occurrence of breast cancer and the search for new therapeutic targets provide theoretical basis.