Abstract
BackgroundPrevious studies have demonstrated that claudin-6 functions as a cancer suppressor in human MCF-7 breast cancer cells. The growth inhibitory effect could be attributed to inhibition of cell proliferation and induction of apoptosis. The purpose of the current study was to examine the involvement of apoptosis signal-regulating kinase 1 (ASK1) in the anticancer effect of claudin-6.MethodsImmunohistochemical analysis was performed to evaluate the ASK1 protein expression and the correlation between ASK1, claudin-6 and clinicopathological features in 85 samples of breast invasive ductal carcinomas (IDC). Western blotting and RT-PCR was carried out to examine the expression of ASK1 and claudin-6 in MCF-7 cell clones transfected with claudin-6.ResultsImmunohistochemical analysis showed that ASK1 expression was significantly related with that of claudin-6 in breast invasive ductal carcinomas (P < 0.05). In addition, a positive correlation between ASK1 and C-erb B 2 protein expression was identified (P < 0.05). Western blotting and RT-PCR consistently revealed that the level of ASK1 protein and mRNA was upregulated in MCF-7 cell clones transfected with claudin-6.ConclusionsOur data suggests, for the first time, that the ASK1 signal may play a positive role in the inhibitory effect of claudin-6 in breast cancer.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1200314318763661
Highlights
Previous studies have demonstrated that claudin-6 functions as a cancer suppressor in human MCF-7 breast cancer cells
apoptosis signal-regulating kinase 1 (ASK1) protein was evaluated in the cytoplasm of breast cancer (Figure 1A), and the positive expression of ASK1 protein was found in 30.59% (26/85) of breast invasive ductal carcinomas (IDC)
We found that ASK1 had relationship with C-erb B 2 protein expression (P = 0.017)
Summary
Previous studies have demonstrated that claudin-6 functions as a cancer suppressor in human MCF-7 breast cancer cells. The purpose of the current study was to examine the involvement of apoptosis signal-regulating kinase 1 (ASK1) in the anticancer effect of claudin-6. We found that claudin-6 is preferentially expressed in mammary epithelial cells and functions as a potential breast cancer suppressor gene [20], which is supported by the follow-up study of Osanai [21]. A previous study has described that breast cancer tissues expressed lower levels of ASK1 compared with normal mammary tissues [23]. The purpose of the current study is to discover the relationship between ASK1 and claudin-6 in breast cancer and to explore the pathways involves the activation of ASK1
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