Kimberly Walter

Introduction. Breast cancer is the leading cause of female cancer mortality worldwide¹. Overall, 1 out of every 8 women in the US will be diagnosed with breast cancer during her lifetime¹. Some known risk factors linked to breast cancer include age, race, hormone usage, tobacco, fitness, and diet¹. Studies show a correlation between specific amounts of daily alcohol consumption and increased risk of breast cancer^2,3. For instance, breast cancer risk increases 4-15% with light consumption of alcohol (<1 drink a day) and increases 7-10% for every 10g of alcohol (about one drink) consumed per day¹. Furthermore, it appears that ethanol only stimulates proliferation in ER⁺, and not ER^– breast cancer cells.⁴ However, the specific mechanism in which alcohol contributes to this increased risk has not been defined and is not completely understood^1,5. Methods. To investigate the mechanism by which alcohol promotes cell transformation, MCF-7 breast cancer cells were incubated with various concentrations of ethanol. Western blot analysis was performed to assess expression of JNK1, pJNK1, and Brf1⁶. Similarly, to investigate the effects of Pol III gene transcription and deregulation, MCF-7 cells were incubated with ethanol, which more than doubled the amounts of Pol III transcripts (specifically pre-tRNA and 5S-rRNA) detecteded⁶. Finally, long-term ethanol exposure was assessed utilizing MCF-7 cells exposed to ethanol for 4 weeks and then transferred to a soft agar assay to measure anchorage-independent growth⁷. Results. Alcohol increases transcription of Brf1 in ER⁺ breast cancer cells by almost 200% via JNK1 activation⁶. Increased Brf1 expression leads to deregulation of RNA Pol III gene transcription^6,8. Deregulation of RNA Pol III allows overexpression of tRNA and 5S rRNA (more than doubling the levels of each of the transcripts), which leads to increased rate and capacity of protein translation within the breast cancer cell⁶. Increased translation promotes cell proliferation and transformation, ultimately leading to a 5.6-fold increase in anchorage-independent growth, and tumor development⁷. Conclusions. The studies provided evidence supporting a specific mechanism of tumor progression in MCF-7 cells due to alcohol exposure that had not previously been hypothesized. These results indicate that the risk of developing breast cancer may be directly increased by drinking alcohol, especially consuming large daily amounts (two drinks or more per day). Increasing public and physician awareness of these findings may help at risk populations, such as women that have higher genetic susceptibility to breast cancer and women who struggle with alcoholism.

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