Study Of Factors Affecting Proliferation,Migration And Chemotherapy Response Of Breast Cancer

Breast cancer is the most common malignant tumor in women,and accounts for about 25% of all female malignant tumors.In recent years,owing to the study of surface receptors in breast cancer,breast cancer was divided into tube cavity tumor,HER-2 positive and basal tumor.Luminal tumors express estrogen receptors and progesterone receptors,but don’t express HER-2;the HER-2 positive type showed no estrogen receptor or progesterone receptor expression;basal tumors have neither estrogen receptor expression,progesterone receptor or HER-2 expression,and is also called as "three negative" breast cancer.The prognosis of breast cancer was closely related with pathological classification and the expression of hormone receptors.Study the biological characteristics of breast cancer cells will improve the therapeutic effect of patients.At present,there are still divergence in some valuable molecular markers in breast cancer,such as Ki-67,which has been identified as an efficient molecular marker for cell proliferation.Ki-67 is a nucleus antigen related to cell-proliferation,it is expressed in every period of cell cycle besides G0 period.It has been identified as the effective molecular marker of cell proliferation.Studies have shown that Ki-67 is related with proliferation activity,tumor differentiation,invasion,metastasis and prognosis.However,the relationship between the expresion of Ki-67 in lumen breast cancer and its clinical significance is still controversial.For these reasons,the first part of this study discussed the expression of Ki-67 in the patients with lumen breast cancer and its relationship with clinical pathological data.A total of 62 lumen breast cancer patients were enrolled in this study.Samples were also obtained from age-matched controls with simple hyperplasia of mammary glands.Fluorescence quantitative PCR method was used to evaluate the expression of Ki-67.Compared with contrast,the expression of Ki-67 in the cancer tissue and serum of breast cancer patients significantly increased(P < 0.05).The level of Ki-67 mRNA in the cancer tissues was also significantly increased compare to that in peritumoral tissues(P < 0.05).In addition,the high expression of Ki-67 in breast cancer tissues was positive correlated with clinical stage,tumor size and lymph node metastases(P < 0.05).The proliferation activity and migration of MCF-7 cells in which the expression of Ki-67 were decreased(P < 0.05).The results showed that Ki-67 can affect the occurrence and development of breast cancer by promotes the proliferation and migration of cancer cells.Further we studied the effect of glutathione S transferase(GST)polymorphism on prognosis of breast cancer.We analyzed polymorphism in GSTM1,GSTT1 and GSTP1 IIe105 Val using restriction fragment length polymorphism combined with polymerase chain reaction(PCR).The results showed that the GG genotype of GSTP1 IIe105 Val had a good response to chemotherapy and a longer survival time compared to wild-type genotype.Furthermore,we carried out a basic study on the related factors of breast cancer treatment response..In this study we found the expression of HER-2 and TOP2 A had effect on breast cancer radiation sensitivity.To explain the influence of HER-2 and TOP2 A on radiation sensitivity of breast cancer,we build recombinant plasmid contains HER-2 or TOP2 A shRNA,to knock down the expression of HER-2 and TOP2 A.After 2 days,protein imprinting was used to test the effect of interference,flow cytometry and MTT was used to detect the expression of Caspase 3,Bcl-2 and Ki-67.Clone formation was used to test the radiosensitivity.The apoptosis rate of SK-Br-3 which HER-2 and TOP2 A had been knocked down increased after radiation treatment,the increment rate was reduced.Caspase 3 which is a marker of apoptosis was increased,Bcl-2 and Ki-67 were decreased.After we knock down HER-2 and TOP2 A at the same time,they elicit synergies.The mechanism of action may be associated with the pathways of Caspase 3,Bcl-2 and Ki-67.These studies provide new molecular indicators and optimization strategies for the clinical diagnosis and treatment of breast cancer.Our work is of relative high application value.