Abstract
Acrylamide (AA) and glycidamide (GA) can be produced in carbohydrate-rich food when heated at a high temperature, which can induce a malignant transformation. It has been demonstrated that GA is more mutagenic than AA. It has been shown that the proliferation rate of some cancer cells are increased by treatment with GA; however, the exact genes that are induced by GA in most cancer cells are not clear. In the present study, we demonstrated that GA promotes the growth of prostate cancer cells through induced protein expression of the cell cycle regulator. In addition, we also found that GA promoted the migratory ability of prostate cancer cells through induced epithelial-to-mesenchymal transition (EMT)-associated protein expression. In order to understand the potential prognostic relevance of GA-mediated regulators of the cell cycle and EMT, we present a three-gene signature to evaluate the prognosis of prostate cancer patients. Further investigations suggested that the three-gene signature (CDK4, TWIST1 and SNAI2) predicted the chances of survival better than any of the three genes alone for the first time. In conclusion, we suggested that the three-gene signature model can act as marker of GA exposure. Hence, this multi-gene panel may serve as a promising outcome predictor and potential therapeutic target in prostate cancer patients.
Highlights
Certain substances in diets, such as acrylamide (AA) and glycidamide (GA), have been reported to induce malignant transformations [1,2]
These results showed that GA promotes cell growth and migration and contributes to malignant phenotypes of prostate cancer cells
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Summary
Certain substances in diets, such as acrylamide (AA) and glycidamide (GA), have been reported to induce malignant transformations [1,2]. Dietary intake of AA has been associated with a high risk of various of cancers, including brain, lung, breast, colorectal, ovarian, endometrial cancer, and prostate cancers [9,10,11,12,13,14]. The loss of CDH1 (E-cadherin) expression is associated with metastatic progression of prostate cancer [33] These EMT markers have the potential to be significant prognostic factors in predicting prostate cancer survival. We demonstrated that GA-promoted the growth ability of prostate cancer cells through induced protein expression of the cell cycle regulator. We found that GA-promoted the migratory ability of prostate cancer cells through induced epithelial-to-mesenchymal transition (EMT)-associated protein expression. We further investigated the GA-mediated change of the above proteins, which could be used as a biomarker for prostate cancer outcomes
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