Differential expression of the TFIIIB subunits Brf1 and Brf2 in cancer cells

Cabarcas, Stephanie M.; Jacob, Joby; Veras, Ingrid; Schramm, Laura

doi:10.1186/1471-2199-9-74

Cited by 27 publications

(29 citation statements)

References 53 publications

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“…Further supporting its role in oncogenesis, increased TBP expression has been observed in a clinically significant number of human colon cancers (26). Overexpression of Brf1 has also been shown to transform mouse embryo fibroblasts (6), and Brf1 is overexpressed in cervical cancers (27). These results, together with our current studies, support the idea that alcohol-mediated increases in TBP and Brf1 drive alcohol-induced liver disease.…”

Section: Discussionsupporting

confidence: 85%

Alcohol Induces RNA Polymerase III-dependent Transcription through c-Jun by Co-regulating TATA-binding Protein (TBP) and Brf1 Expression

Zhong

Machida²,

Tsukamoto

et al. 2011

Journal of Biological Chemistry

138

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Chronic alcohol consumption is associated with steatohepatitis and cirrhosis, enhancing the risk for hepatocellular carcinoma. RNA polymerase (pol) III transcribes a variety of small, untranslated RNAs, including tRNAs and 5S rRNAs, which determine the biosynthetic capacity of cells. Increased RNA pol III-dependent transcription, observed in transformed cells and human tumors, is required for oncogenic transformation. Given that alcohol consumption increases risk for liver cancer, we examined whether alcohol regulates this class of genes. Ethanol induces RNA pol III-dependent transcription in both HepG2 cells and primary mouse hepatocytes in a manner that requires ethanol metabolism and the activation of JNK1. This regulatory event is mediated, at least in part, through the ability of ethanol to induce expression of the TFIIIB components, Brf1, and the TATA-binding protein (TBP). Induction of TBP, Brf1, and RNA pol III-dependent gene expression is driven by enhanced c-Jun expression. Ethanol promotes a marked increase in the direct recruitment of c-Jun to TBP, Brf1, and tRNA gene promoters. Chronic alcohol administration in mice leads to enhanced expression of TBP, Brf1, tRNA, and 5S rRNA gene transcription in the liver. These alcohol-dependent increases are more pronounced in transgenic animals that express the HCV NS5A protein that display increased incidence of liver tumors. Together, these results identify a new class of genes that are regulated by alcohol through the co-regulation of TFIIIB components and define a central role for c-Jun in this process.

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Section: Discussionsupporting

confidence: 85%

Alcohol Induces RNA Polymerase III-dependent Transcription through c-Jun by Co-regulating TATA-binding Protein (TBP) and Brf1 Expression

Zhong

Machida²,

Tsukamoto

et al. 2011

Journal of Biological Chemistry

138

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“…23 Overexpression of Brf1 transforms mouse embryo fibroblasts 24 and cells in cervical cancers and biopsies of human HCC cases. 25, 26 Our recent studies also indicate that Brf1 is overexpressed in estrogen receptor-positive (ER + ) human breast cancer cases (unpublished).…”

Section: Dysregulation Of Pol III Genes Promotes Cell Transformatimentioning

confidence: 90%

Abnormal expression of TFIIIB subunits and RNA Pol III genes is associated with hepatocellular carcinoma

2017

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The levels of the products of RNA polymerase III-dependent genes (Pol III genes), including tRNAs and 5S rRNA, are elevated in transformed and tumor cells, which potentiate tumorigenesis. TFIIB-related factor 1 (Brf1) is a key transcription factor and specifically regulates the transcription of Pol III genes. In vivo and in vitro studies have demonstrated that a decrease in Brf1 reduces Pol III gene transcription and is sufficient for inhibiting cell transformation and tumor formation. Emerging evidence indicates that dysregulation of Brf1 and Pol III genes is linked to the development of hepatocellular carcinoma (HCC) in humans and animals. We have reported that Brf1 is overexpressed in human liver cancer patients and that those with high Brf1 levels have shorter survivals. This review summarizes the effects of dysregulation of these genes on HCC and their regulation by signaling pathways and epigenetics. These novel data should help us determine the molecular mechanisms of HCC from a different perspective and guide the development of therapeutic approaches for HCC patients.

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“…Previously, we demonstrated differences in RNA pol III transcription in sex-specific cancer cell lines including the breast, cervical and prostate cell lines [20]. Further, RNA pol III transcription has been demonstrated to be regulated by the purified green tea polyphenol EGCG in the HeLa cervical cancer cell line [16].…”

Section: Resultsmentioning

confidence: 99%