The Relationship And Expression Of Tgf-β1,smad4 And Vegf Protein In Breast Carcinoma

[Background and objective]The breast carcinoma is one of the most common malignent tumors in women. Duo to the changes of human's life and diet habits,its incidence increased gradually in recent years and influenced women's health and the quality of life greatly.As we all know,the development of tumor is a complex process,and results from synthetic effects of many factors.A lot of events including signaling transduction pathway,cell proliferation,the regulation of cell cycle,apoptosis and angiogenesis led to tumorgenesis.Today,more and more studies focused on the molecular biological basis of breast carcinoma' development at home and abroad.Transforming growth factor beta(TGF-β)is composed of TGF-βs family,activin/inhibins family,bone morphogenetic proteins(BMPs)family and Mǖllerian inhibinting substance(MIS)family.The numbers of it's member is more than 40.many studies pointed to TGF-β1-5,which play an important role in cell proliferation,different,apoptosis,adhesion,embryogenesis and tissue repair,inflammation and fibrosis.Recently,it has been found that the abnormalities of TGF-βsignaling transduction pathway are related to the tumor's development and metastasis closely. TGF-βsignaling transduction pathway suppresses the cell proliferation.The abnormal changes in TGF-βsignaling transduction pathway result in cell's insensitivities to suppressive effects of TGF-βtransduction pathway.So,cells happen to proliferation uncontrolly,and lead to tumorgenesis.Tumor cells can secret TGF-β to promote the proliferation of vascular endothelia cells,which are benefit to the angiogenesis in tumor tissue.It is reported that overexpression of TGF-β1-3 EGF and FGF has been found in pancreatic carcinoma,and was related to tumor's poor differentiation and lower survival.The higher expression of TGF-β1 was found in many tumors,such as esophageal carcinoma and breast carcinoma,and was related to tumor's clinic stage and lymphatic metastasis closely.Smad4 was found by Hahn in pancreatic carcinoma as a anti-oncogene in 1996, which was located at human chromosome18q21.1.About 90%pancreatic carcinoma patients have been found heterozygous loss of Smad4 in chromosome 18q zone. Smad4 is an important cellar cascade molecular,which transducts TGF-βsignaling.It can form a compound with active activated-receptor Smad and regulates the transcription of TGF-βresponse gene with other transcription factors after translocated to the cell nuclear.The loss of function or lower expression of Smad4 might influence TGF-βsignaling transduction and lead to tumorgenesis.Vascular endothelial growth factor(VEGF) is an important pro-angiogenesis factor.Angiogenesis is utmost importance in promoting tumor growth and metastasis. VEGF can increase proteinases activities to promote mesenchymal degradation.It can also increase vascular permeability.VEGF includes VEGFA B C D E and placental growth factor(PLGF).VEGF C and VEGF D can not only induce angiogenesis,but also induce lymphagiogenesis.It is indicated that the expression of VEGF in tumor is related to microvessel density directly.So,VEGF might become a tumor marker to evaluate breast carcinoma's prognosis.As a transcription factor in TGF-βtransduction pathway,Smad4 gene inactivity will lead to the abnormality of Smad4 protein expression.So,TGF-β/Smad4 signaling transduction net is disorder and loses the inhibition to the proliferation of tumor cells.It is rarely reported about the expression and relationship of TGF-β1,Smad4 and VEGF protein in breast carcinoma.In order to explore the role of TGF-β1, Smad4 and VEGF protein in breast carcinoma'development and metastasis,we detected the expression of TGF-β1,Smad4 and VEGF protein in mastoplasia,breast carcinoma and adjacent tissue by immunchistochemistry assay(SP)in this article,and compared the expression of TGF-β1,Smad4 and VEGF protein between breast carcinoma with lymphatic metastasis group and without lymphatic metastasis group.[Materials and methods]1.Adopt immunohistochemistry assay to detect TGF-β1,Smad4 and VEGF protein expressions in 35 cases of mastoplasia tissue 35 cases of breast carcinoma tissue and 30 cases of adjacent tissue respectively.2.Statistical analysis:Using SPSS13.0 statistical software package.The Chi-square test for rate comparison.Bivariate correlation analysis using Spearman correlation.The level of significant difference isα=0.05.[Results]1.The positive rate of TGF-β1 protein expression was 82.9%in cases of breast carcinoma tissue,14.3%in cases of mastoplasia tissue and 20.0%in cases of adjacent tissue.There was statistic difference between breast carcinoma group and mastoplasia group(χ~2=32.941,P＜0.05).the comparison between breast carcinoma group and adjacent tissue group was statistic difference(χ~2=25.682,P＜0.05).the difference of TGF-β1 protein expression between mastoplasia group and adjacent tissue group was'nt statistic significance(χ~2=0.375,P＞0.05).The positive rate of TGF-β1 protein expressions in breast carcinoma group without lymph node metastasis and group with lymph node metastasis were 55.6%and 92.3%respectively.There was statistic significance between two groups(P＜0.05).2.The positive rate of Smad4 protein expression was 25.7%in cases of breast carcinoma tissue,88.6%in cases of mastoplasia tissue and 80.0%in cases of adjacent tissue.There was statistic difference between breast carcinoma group and mastoplasia group(χ~2=28.233,P＜0.05).the comparison between breast carcinoma group and adjacent tissue group was statistic difference(χ~2=19.046,P＜0.05).the difference of Smad4 protein expression between mastoplasia group and adjacent tissue group was'nt statistic significance(χ~2=0.912,P＞0.05).The positive rate of Smad4 protein expressions in breast carcinoma group without lymph node metastasis and group with lymph node metastasis were 33.3%and 23.1%respectively.There was'nt statistic significance between two groups(P＜0.05). 3.The positive rate of VEGF protein expression was 88.6%in cases of breast carcinoma tissue,54.3%in cases of mastoplasia tissue and 53.3%in cases of adjacent tissue.There was statistic difference between breast carcinoma group and mastoplasia group(χ~2=10.08,P＜0.05).the comparison between breast carcinoma group and adjacent tissue group was statistic difference(χ~2=10.01,P＜0.05).the difference of VEGF protein expression between mastoplasia group and adjacent tissue group was'nt statistic significance(χ~2=0.006,P＞0.05).The positive rate of VEGF protein expressions in breast carcinoma group without lymph node metastasis and group with lymph node metastasis were 66.7%and 96.2%respectively.There was statistic significance between two groups(P＜0.05).4.There was a negative correlation between expressions of TGF-β1 protein and Smad4 protein(γ=-0.426,P＜0.05).5.There was a positive correlation between expressions of TGF-β1 protein and VEGF protein(γ=0.559,P＜0.05).6.There was a negative correlation between expressions of Smad4 protein and VEGF protein(γ=-0.61,P＜0.05).[Conclusions]1.The higher expression of TGF-β1 protein is related to the occurence, development and metastasis of breast carcinoma.2.The lower expression of Smad4 protein is related to the occurence, development of breast carcinoma.3.The abnormalities of TGF-β1/Smad4 signaling transduction pathway play a role in the occurence and development of breast carcinoma.4.VEGF protein is related to the occurence and development and metastasis of breast carcinoma.5.TGF-β1 and VEGF can promote the development and metastasis of breast carcinoma synergistically.