Objective To investigate the effects of autophagy on breast cancer cells to tamoxifen resist-ance.Methods Immunofluorescence was used to count the proportion of the cells with autophagy in MCF -7 and MCF-7/TAMR,as well as ,the average of autophagosome in each cells .Western blotting was used to detect the different expressions of p38,c-jun and LC3 in MCF-7 and MCF-7/TAMR.Stepwise selection was used to detect the duration of resistance to different doses of tamoxifen when upregulating or downregulating of LC 3.West-ern blot was facilitated to investigate changes of activity of p 38/c-jun.Rusults Compared with MCF -7,the proportion of the cells with autophagosome in MCF -7/TAMR was markedly increased ,the same as the average of autophagosome in each cells .Compared with MCF-7,LC3,especially LC3IIprotein expressive levels in MCF -7/TAMR was significantly increased .The expressive level of LC3 during the induction process of TAM resistance was negative correlated with resistant cell lines .The expressions of phosphorylated p 38 and c-Jun in MCF-7/TAMR were significantly increased .Conclusion Autophagy promotes breast cancer cells to resistant to tamox-ifen,due to downregulation of the expression of autophagy related proteins which may inhibit the generation of re -sistant breast cancer cells .This may be a viable treatment strategy for refractory breast cancer .

Recently,in the management of estrogen receptor(ER)positive breast canner,endocrine thera-py is the main treatment method;and estrogen receptor -α( ER-α) has obtained popularity as one of the most common targets .There are many known risk factors for ER function in breast canner such as ER gene mutation ;unbalanced microenvironment;signal transduction pathway disorders .While more and more attention is paid to the changes in ER expression and function induced by epigenetic aberrations .ER gene promoter methylation induces down regulation and deletion in ER expression ,which has not only a most highly incidence in epigenetic aberra-tions,but also a widen degree of research .Histone modification could influence ER -αexpression and function , either.However,the special mirco RNAs(miRNAs)are also implicated in the regulation of ER -α,and affect the therapy of tamoxifen in breast tumor .

Breast cancer is one of the most common malignant tumors in women.Early diagnosis plays a very important role in the treatment of breast cancer.Recently,with the development of epigenetics,it gives us a new orientation for early detection for cancers.The most understood mechanism of epigenetics is DNA methyla-tion.Ras associated domain family 1A gene(RASSFlA)promoter methylation occurres in tumor′s early stage,and have a statistically concern with tumor′s TNM stage,invasiveness and outcomes.Moreover,DNA methylation can be reversed,so RASSF1A can be a promising candidate for early breast cancer detection biomarker,and can be a potential orientation for breast cancer treatment.