论文部分内容阅读
Tumor necrosis factor-α(TNF-α), a pleiotropic cytokine, exists in two biological forms, namely a 26kD transmembrane TNF-α(TM-TNF-α) and a 17kD secreted TNF-α(S-TNF-α).However, the role of TTM-TNF-αn cancer is unclear.Using a monoclonal antibody specific to TM-TNF-α to check 39 patients with breast cancer, we found a high expression of TM-TNF-α with 93.3% positive rate and a close association between the expression of TM-TNF-α at high level and lymphatic metastasis.In addition, the expression of breast cancer biomarkers, Her-2 and NF-κB, are also related to the expression of TM-TNF-α, but PR and ER are not.These results suggest that TM-TNF-α may play an important role in the development of breast cancer.In vitro, MDA-MB-231 with expression of TM-TNF-α at high level has been shown to be resistant to Adriamycin, while MCF-7 cells with expression of TTM-TNF-α at low level were sensitive to the same drug.We silenced TM-TNF-α expression in MDA-MB-231 or transfected a TM-TNF-α mutant which is deletion of TNF receptor binding segment into MCF-7 cells, the former became sensitive to, but the latter resistant to Adriamycin.These data imply the contribution of TM-TNF-α to the chemoresistance of breast cancer.As our results point out TM-TNF-α as a tumor marker, we used TM-TNF-α McAb to kill MDA-MD-231 in nude mice.This antibody has been shown to induce significant tumor regression and inhibit tumor metastasis, indicating that TM-TNF-α may be a novel tumor marker and a potent promising target for breast cancer therapy.