Expression Of STAT3 Gene In Breast Carcinoma And Its Clinical Significance

Background and ObjectivesBreast cancer has the highest incidence of all types of malignant cancer in women,and can metastasia to axillary nodes ,marrow,bronchus,lung and so on.Breast carcinoma threated the life of patients severitly.The incidence is much more higher in china recently because of improving of the live standard and simplification of family composition.Breast cancer is thought to be multiple factor and the process of multimutated accumulation,but cause of the disease is not clear.Recently the research in the origin and the development of breast carcinoma is always a hot spot in the domain.And it is also a focus that reasearch the related protein with overexpression and abnormal activation in the metastasis process of breast carcinoma.Recently signal transducer and activator of transcription 3(STAT3) has been recognized as a kind of critical nuclear factor.Compared with normal cells and tissues,constitutively activated STATs have been detected in a wide variety of human cancer cell lines and multituded malignant tumors.Signal transducer and actlvator of transcription 3(STAT3)can be activated by cytokines and growth factors,and activation of STAT3 is involved in modulating cell proliferation,differentiation and apoptosis.STAT3 has been classified as an oncogene because STAT3 can mediate malignant transformation of cultured cells.The abnormal expression and activity enhancement of STAT3 has been detected in many multituded malignant tumors and cell lines such as pate carcinoma,breast carcinoma and prostate carcinoma.The mRNA expression of STAT3 gene were detected in 32 cases of breast carcinoma and 10 cases of benign mammary lesions by fluorescent real-time RT-PCR,45 cases of parafine-embedded speciments of breast carcinoma were studied by immunohistochemical study.Statistical analysis was carried out to analyze whether the expression of STAT3 gene is relatede to histologic type and lymph node metastases and the level of ER,PRandCerbB-2.MethodsThe mRNA expression of STAT3 gene were detected in 32 cases of breast carcinoma and 10 cases of benign mammary lesions by fluorescent real-time RT-PCR,Which take SYBR Green I as fluorescent dye and house-keeping gene as intra-control.Statistical analysis was carried out to analyze the correlation between STAT3 gene expression and clinical significance in these breast cancer patients on the transcriptional level.The protein expression of p-STAT3 were detected in 45 cases of parafine-embedded speciments of breast carcinoma and 12 cases of tissues in carcinoma side by immunohistochemical study. Statistical analysis was carried out to analyze the correlation between STAT3 gene expression and clinical significance in these breast cancer patients on the protein level.ResultsThe relative expression level of STAT3 mRNA.and protein:(1)STAT3 gene was expression in 2 speciments of 12 cases of benign mammary lesions(16.7%),the relative expression level of STAT3 mRNA were 5.96E-03±3.05E-03,in contrast to 27 speciments of 45 cases of breast carcinoma(60%),the relative expression level of STAT3 mRNA were 33.95E-03±17.37E-03 which expression was significantly higher in the other group (P<0.01)(2)STAT3 gene was expression in 13 speciments of 27 cases of lymph node-negative(48.1%), the relative expression level of STAT3 mRNA were 26.21E-03±13.11E-03,in contrast to 14 speciments of 18 lymph node-positive(77.8%), the relative expression level of STAT3 mRNA were38.61E-03±18.23E-03 which expression was significantly higher in the other group(P<0.05).(3)STAT3 gene was expression in 6 speciments of 16 cases of PR negative (37.5%),the relative expression level of STAT3 mRNA were 28.26E-03±10.11E-03,in contrast to 21 speciments of 29 PR positive(72.3%),the relative expression level of STAT3 mRNA were 39.49E-03±19.41E-03 which expression was significantly higher in the other group (P<0.05).(4)Neither mRNA nor protein expression of STAT3 gene correlated with age of patients,size of tumor, the level of ER and CerbB-2.(P > 0.05)ConclusionsAs an oncogene, STAT3 participated in the carcinogenesis,development and prognosis of breast carcinoma.The expression of STAT3 possibly regulated by the progestin,but was not associated with the Estrogen and CerbB-2.STAT3 maybe a kind of related gene which participated in the invasion process of breast carcinoma and regulated by the progestin,and it is a point where signal conduction pathway with many kinds of cytokine in breast cancer cell.To enforce the intervention on the signal conduction with STAT3 will certainly to induce the apotosis in breast cancer cell,inhibiting proliferation,and inhibiting tumor angiogenensis.It is valuable for the early diagnosis and prognosis judgement in breast carcinoma through detected the level of STAT3 quantitatly.