癌基因Stat3在人乳腺癌发生发展中的作用

The role of oncogene Stat3 in carcinogenesis and progression of human breast cancer

Objective The aim of this study is to investigate STAT3 expression and the relationship between protein levels of STAT3 and clinicopathological parameters together with preoperative chemotherapy in human breast cancer. Methods Samples were obtained from 51 patients with breast carcinoma in which 7 patients had received preoperative chemotherapy. Western blot was used to measure the protein expression in tissue and SK-BR-3 cell line. MTT method was used to evaluate the proliferation. Cell-cycle and apoptosis were quantified by flow cytometry. Results STAT3 protein levels increased in breast cancer tissues compared with adjacent normal tissues(t=5.540,P<0.01); Overexpression of STAT3 was significantly correlated with TNM staging and lymph node metastasis(t=2.160,P<0.05);The expression of STAT3 protein in the ER and PR negative patients was higher than that in the ER and PR positive ones (t=3.401, P<0.05).STAT3 protein levels in patients who received preoperative chemotherapy were lower than that in the patients who did not(t=2.07,P<0.05).AG490 could downregulate JAK2, STAT3, p-STAT3 and Bcl-x L protein expression and could inhibit proliferation and augment apoptosis of SK-BR-3 cell. Conclusions The constitutive activation of STAT3 pathway may play an essential role in the tumorigenesis and progression of human breast cancer. Neoadjuvant chemotherapy can inhibit STAT3 expression. Blocking STAT3 pathway can inhibit the proliferation, augment the apoptosis of human breast cancer cells.