Alcohol has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC). Studies have demonstrated that alcohol intake increases the risk of breast cancer, and alcohol also stimulates breast cancer cell growth. Deregulation of Pol III genes is tightly associated with tumour development. Transcription factor II-B (TFIIB)-related factor 1 (Brf1) is a transcription factor that specifically regulates Pol III gene transcription. Our in vivo and in vitro studies have indicated that alcohol enhances the transcription of Pol III genes to cause an alteration of cellular phenotypes, which is closely related with human breast cancer. Betaine is a vegetable alkaloid and has antitumor functions. Most reports about betaine show that the consumption level of betaine is inversely associated with a risk of breast cancer. Although different mechanisms of betaine against tumour have been investigated, nothing has been reported on the effect of betaine on the deregulation of Brf1 and Pol III genes. In this study, we determine the role of betaine in breast cancer cell growth and colony formation and explore its mechanism. Our results indicate that alcohol increases the rates of growth and colony formation of breast cancer cells, whereas betaine is able to significantly inhibit the effects of alcohol on these cell phenotypes. Betaine decreases the induction of Brf1 expression and Pol III gene transcription caused by ethanol to reduce the rates of cell growth and colony formation. Together, these studies provide novel insights into the role of betaine in alcohol-caused breast cancer cell growth and deregulation of Brf1 and Pol III genes. These results suggest that betaine consumption is able to prevent alcohol-associated human cancer development.

中文翻译：

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甜菜碱在抑制酒精引起的 RNA Pol III 基因转录和细胞生长的诱导中的作用。

酒精已被国际癌症研究机构 (IARC) 列为人类致癌物。研究表明，饮酒会增加患乳腺癌的风险，而酒精也会刺激乳腺癌细胞的生长。Pol III 基因的失调与肿瘤发展密切相关。转录因子 II-B (TFIIB) 相关因子 1 (Brf1) 是一种专门调节 Pol III 基因转录的转录因子。我们的体内和体外研究表明，酒精会增强 Pol III 基因的转录，从而引起细胞表型的改变，这与人类乳腺癌密切相关。甜菜碱是一种植物生物碱，具有抗肿瘤作用。大多数关于甜菜碱的报告表明，甜菜碱的摄入量与患乳腺癌的风险呈负相关。尽管已经研究了甜菜碱抗肿瘤的不同机制，但没有关于甜菜碱对 Brf1 和 Pol III 基因失调的影响的报道。在这项研究中，我们确定了甜菜碱在乳腺癌细胞生长和集落形成中的作用，并探讨了其机制。我们的研究结果表明，酒精会增加乳腺癌细胞的生长速度和集落形成，而甜菜碱能够显着抑制酒精对这些细胞表型的影响。甜菜碱降低由乙醇引起的 Brf1 表达和 Pol III 基因转录的诱导，从而降低细胞生长和集落形成的速率。总之，这些研究为甜菜碱在酒精引起的乳腺癌细胞生长和 Brf1 和 Pol III 基因失调中的作用提供了新的见解。