Abstract
Background
Esophageal cancer is a lethal malignancy with a poor prognosis. The incidence of esophageal adenocarcinoma, which develops from Barrett’s esophagus (BE), has recently been increasing. In a previous study, we found that PDZK1 expression is higher in long segment BE compared to that in short-segment BE. However, the function of PDZK1 in the mucosa of BE is unclear.
Aims
Clarify the role of PDZK1 in BE mucosa using PDZK1 overexpressed cells.
Methods
Human adenocarcinoma-derived OE33 cells were used as a parental cell line and transfected to generate PDZK1 overexpressed OE33 cells (PC cells) or transfected with empty vector as control cells (NC cells). Cell growth of NC and PC cells in 10% fetal bovine serum was evaluated by cell counting. The effect of PDZK1 on proteasome inhibitor (PSI)-induced apoptosis was qualified by fluorescence microscopy and quantified by flow cytometry. Expression of apoptosis-related proteins was evaluated by western blotting.
Results
There were no significant differences in cell growth between NC and PC cells. PSI significantly increased apoptosis in NC cells, but not in PC cells. In response to PSI, increased levels of cleaved-caspase3 and decreased pro-caspase3 levels were found in NC cells, but not in PC cells. In NC cells, PSI significantly decreased Bcl-2 expression without affecting Bax levels. In contrast, high expression of both Bcl-2 and Bax was observed in PC cells.
Conclusion
Overexpression of PDZK1 protein induces an apoptosis-resistant phenotype in BE cells, which may be a potential therapeutic target.
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Acknowledgements
We would like to express sincere appreciation to Ms. Kimiko Hagihara, B.N.S, for her technical support. We would also like to thank Editage (www.editage.com) for English language editing.
Funding
This study was supported by JSPS KAKENHI (C) Grant Number JP (17K09364) to TM.
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OH, AS, and KG contributed substantially to the conception or design of the work and the acquisition, analysis and interpretation of the data. KG, YH, SF, MO, TM, and HM collected data in this study. OH drafted the manuscript and AS, EU, YF, and KN critically revised it for important intellectual content. All authors approved the final version to be published and agreed to be accountable for all aspects of the work, including to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Handa, O., Goda, K., Handa, Y. et al. PDZK1 induces resistance to apoptosis in esophageal adenocarcinoma cells. Esophagus 18, 655–662 (2021). https://doi.org/10.1007/s10388-021-00819-z
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DOI: https://doi.org/10.1007/s10388-021-00819-z