Anti-apoptotic effect of claudin-1 in tamoxifen-treated human breast cancer MCF-7 cells

Human breast cancer MCF-7 and T47 D cells were treated with or without tamoxifen, siRNA against claudin-1, or tamoxifen and claudin-1 siRNA. The samples were analyzed by RT-PCR, Western blotting or immunofluorescent staining.The expression of claudin-1 was upregulated in tamoxifen-treated MCF-7 cells, whereas the expression of claudin-1 was not altered in tamoxifen-treated T47 D cells. Knockdown of claudin-1 by siRNA increased the amount of poly (ADP-ribose) polymerase (PARP) regardless of tamoxifen treatment in MCF-7 cells, but not T47 D cells. In the cell membranes of the MCF-7 cells, tamoxifen treatment increased the amount of claudin-1, but decreased the amount of β-catenin. Claudin-1 siRNA increased the amount of E-cadherin in the cytoplasm of the MCF-7 cells as well as the amount of β-catenin in their cell membranes.These results indicate that claudin-1 has anti-apoptotic effects, and is involved in the regulation of the expression and subcellular localization of β-catenin and E-cadherin in MCF-7, but not T47 D cells.Breast cancer is the second most common cause of female mortality in United States. The breast cancer incidence and mortality rates were about 190,000 and 40,000, respectively, in 2009 [1]. The majority of breast cancers are sporadic, and most risk factors for the disease are related to estrogen exposure. This suggests that insufficient apoptosis in cancer cells is involved in their survival as insuffcient apoptosis leads to the development of chemotherapy resistance and carcinogenesis [2].Tamoxifen is one of most widely used anti-estrogen drugs for the treatment of human breast cancer [3]. Tamoxifen treatment leads to a rapid decrease in number of S-phase cells, an accumulation of cells in the G1-fraction [4], and the induction of apoptosis in vivo and vitro [5-7]. Tamoxifen induces apoptosis through several distinct pathways including a mitochondria-dependent pathway, the induction of c-Myc, the activation of members of the mitogen-activated pro