Alcohol Intake and Abnormal Expression of Brf1 in Breast Cancer

Abstract

Breast cancer is the most common malignant disease of females. Overall, one woman in every nine will get breast cancer at some time in her life. Epidemiological studies have indicated that alcohol consumption has most consistently been associated with breast cancer risk. However, the mechanism of alcohol-associated breast cancer remains to be addressed. Little is known about the effects of alcohol consumption on Brf1 (TFIIIB-related factor 1) expression and RNA Pol III gene (RNA polymerase III-dependent gene) transcription, which are responsible for protein synthesis and tightly linked to cell proliferation, cell transformation, and tumor development. Emerging evidences have indicated that alcohol induces deregulation of Brf1 and Pol III genes to cause the alterations of cell phenotypes and tumor formation. In this paper, we summarize the progresses regarding alcohol-caused increase in the expression of Brf1 and Pol III genes and analysis of its molecular mechanism of breast cancer. As the earlier and accurate diagnosis approach of breast cancer is not available yet, exploring the molecular mechanism and identifying the biomarker of alcohol-associated breast cancer are especially important. Recent studies have demonstrated that Brf1 is overexpressed in most ER+ (estrogen receptor positive) cases of breast cancer and the change in cellular levels of Brf1 reflects the therapeutic efficacy and prognosis of this disease. It suggests that Brf1 may be a potential diagnosis biomarker and a therapeutic target of alcohol-associated breast cancer.

Mitogen- and Stress-Activated Protein Kinase 1 Mediates Alcohol-Upregulated Transcription of Brf1 and tRNA Genes to Cause Phenotypic Alteration

“…Chronic alcohol consumption causes liver fibrosis and cirrhosis and enhances the risk of HCC [ 33 ]. Alcohol was classified as carcinogenic by the International Agency for Research on Cancer (IARC) [ 34 – 37 ]. Here, our study indicates that the alcohol-fed HCV-NS5A transgenic mouse increases Brf1 and Pol III gene transcription to facilitate liver tumor development (Figures 7(c) and 7(d) ).…”

Exploring the Role and Mechanism of pAMPKα‐Mediated Dysregulation of Brf1 and RNA Pol III Genes

“…Our earlier studies have demonstrated that alcohol increases Brf1 expression in tissue culture and animal models, which facilitates cell proliferation and transformation, and tumor formation [ 15 , 17 , 19 , 20 , 29 – 32 ]. Chronic alcohol consumption results in the production of acetaldehyde and CYP2E1 induction (Cytochrome P450 2E1) [ 14 ]. Acetaldehyde is a by-product of alcohol metabolism catalyzed by ADH (alcohol dehydrogenase), which has direct mutagenic and carcinogenic effects in vitro and in vivo [ 14 , 33 ].…”

“…Chronic alcohol consumption results in the production of acetaldehyde and CYP2E1 induction (Cytochrome P450 2E1) [ 14 ]. Acetaldehyde is a by-product of alcohol metabolism catalyzed by ADH (alcohol dehydrogenase), which has direct mutagenic and carcinogenic effects in vitro and in vivo [ 14 , 33 ]. CYP2E1 is associated with the release of ROS (reactive oxygen species) and conversion of procarcinogens to carcinogens [ 14 ].…”

“…Acetaldehyde is a by-product of alcohol metabolism catalyzed by ADH (alcohol dehydrogenase), which has direct mutagenic and carcinogenic effects in vitro and in vivo [ 14 , 33 ]. CYP2E1 is associated with the release of ROS (reactive oxygen species) and conversion of procarcinogens to carcinogens [ 14 ]. Alcohol exposure increases cellular production of ROS, causing cellular stress to result in tissue injury and diseases [ 14 ].…”

“…CYP2E1 is associated with the release of ROS (reactive oxygen species) and conversion of procarcinogens to carcinogens [ 14 ]. Alcohol exposure increases cellular production of ROS, causing cellular stress to result in tissue injury and diseases [ 14 ]. ROS-induced oxidative stress activates the JNK1 pathway to increase Brf1 expression [ 31 ].…”