Abstract P5-08-24: How do real-world treatment patterns compare to guideline recommendations for first-line metastatic breast cancer patients in US community clinics?

Epidemiological studies have indicated that alcohol consumption is an established risk factor for breast cancer. The association of alcohol consumption and breast cancer is more pronounced in ER+ cases than in ER- cases. However, this molecular mechanism remains to be determined. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular tRNAs and 5S rRNA production, increasing translational capacity to promote cell transformation and tumor formation. Our results reveal that alcohol increases Pol III gene transcription in both normal and cancer breast cell lines. The induction of Pol III genes by alcohol in ER+ breast cancer cells is significantly higher than in ER- normal breast cells and ER- breast cancer cells. E2 causes slight increase in Pol III gene transcription. The addition of ethanol to this system produces a marked increase. Alcohol increases ERa expression to enhance the cellular levels of Brf1 protein and mRNA. In addition, ethanol markedly stimulates phosphorylation of JNK1. Inhibition of JNK1 decreases ERE-Luc reporter activity and represses expression of ERa, Brf1 and Pol III genes. Reduction of ERa by its siRNA represses Brf1 and Pol III gene transcription. Ethanol with E2 produces larger and more numerous colonies. Repression of ERa or Brf1 inhibits alcohol-induced cell transformation. More interestingly, human biopsies studies show that Brf1 expression is significantly increased in nuclei of breast cancer cells, compared to tissue adjacent...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research