Oncotarget

Research Papers:

Tamoxifen represses alcohol-induced transcription of RNA polymerase III-dependent genes in breast cancer cells

Qian Zhong, Ganggang Shi, Qingsong Zhang, Lei Lu, Daniel Levy and Shuping Zhong _

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Oncotarget. 2014; 5:12410-12417. https://doi.org/10.18632/oncotarget.2678

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Abstract

Qian Zhong1,2, Ganggang Shi3, Qingsong Zhang1, Lei Lu1, Daniel Levy1 and Shuping Zhong1,3

1 Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

2 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, China

3 Shantou University Medical College, Shantou, Guangdong, China

Correspondence:

Shuping Zhong, email:

Keywords: Tamoxifen, Alcohol, Estrogen receptor, C-Jun, Brf1, Pol III genes, Breast cancer

Received: August 23, 2014 Accepted: November 04, 2014 Published: November 04, 2014

Abstract

Alcohol consumption in women has been associated with an increased risk of breast cancer, particular in estrogen receptor positive (ER+) cases. Deregulation of RNA polymerase III-dependent (Pol III) transcription enhances cellular tRNAs and 5S rRNA production, leading to an increase in translational capacity to promote cell transformation and tumor formation. Our recent studies demonstrated that alcohol induces Brf1 expression and Pol III gene transcription via ER. Here, we report that Tamoxifen (Tam) inhibits the induction of Brf1 and Pol III genes in ER+ breast cancer cells. Further analysis indicates that alcohol increases c-Jun expression to upregulate the transcription of Brf1 and Pol III genes, whereas Tam reduces c-Jun expression to repress the transcription of Brf1. Repression of cJun decreases cellular levels of ERα and Brf1. Alcohol-dependent increased occupancy of Brf1 in Pol III gene promoters is reduced by Tam. The repression of Brf1 and Pol III genes by Tam reduces alcohol-induced cell proliferation and colony formation. Together, these results indicate that Tam inhibits alcohol-induced Brf1 expression through c-Jun and ERα to downregulate Pol III gene transcription. Our studies uncover a new mechanism of Tam-treated ER+ breast cancer, by which Tam inhibits tumor growth through repressing Pol III gene transcription.


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