Tamoxifen represses alcohol-induced transcription of RNA polymerase III-dependent genes in breast cancer cells.
Tamoxifen represses alcohol-induced transcription of RNA polymerase III-dependent genes in breast cancer cells.
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DOI：
10.18632/oncotarget.2678
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发表时间：
2014-12-15
期刊：
影响因子：
--
通讯作者：
Zhong S
中科院分区：
文献类型：
--
作者：
Zhong Q;Shi G;Zhang Q;Lu L;Levy D;Zhong S
女性饮酒与乳腺癌风险增加有关，尤其是雌激素受体阳性（ER+）病例。RNA聚合酶III依赖（Pol III）转录的解除会增强细胞tRNAs和5S rRNA的产生，从而导致翻译能力的增加，从而促进细胞转化和肿瘤形成。我们最近的研究表明，酒精通过内质网诱导Brf1表达和Pol III基因转录。在这里，我们报道了他莫昔芬（Tam）抑制ER+乳腺癌细胞中Brf1和Pol III基因的诱导。进一步分析表明，酒精增加c-Jun表达上调Brf1和Pol III基因的转录，而Tam降低c-Jun表达抑制Brf1的转录。cJun的抑制降低了ERα和Brf1的细胞水平。在Pol III基因启动子中Brf1的酒精依赖性增加占用被Tam减少。Tam对Brf1和Pol III基因的抑制可减少酒精诱导的细胞增殖和集落形成。总之，这些结果表明Tam通过c-Jun和ERα抑制酒精诱导的Brf1表达，下调Pol III基因转录。我们的研究揭示了Tam治疗ER+乳腺癌的新机制，Tam通过抑制Pol III基因转录抑制肿瘤生长。
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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影响因子：
8.8
作者：
Beral, V;Hamajima, N;Hirose, K;Rohan, T;Calle, EE;Heath, CW;Coates, RJ;Liff, JM;Talamini, R;Chantarakul, N;Koetsawang, S;Rachawat, D;Morabia, A;Schuman, L;Stewart, W;Szklo, M;Bain, C;Schofield, F;Siskind, V;Band, P;Coldman, AJ;Gallagher, RP;Hislop, TG;Yang, P;Kolonel, LM;Nomura, AMY;Hu, J;Johnson, KC;Mao, Y;De Sanjose, S;Lee, N;Marchbanks, P;Ory, HW;Peterson, HB;Wilson, HG;Wingo, PA;Ebeling, K;Kunde, D;Nishan, P;Hopper, JL;Colditz, G;Gajalakshmi, V;Martin, N;Pardthaisong, T;Solpisornkosol, S;Theetranont, C;Boosiri, B;Chutivongse, S;Jimakorn, P;Virutamasen, P;Wongsrichanalai, C;Ewertz, M;Adami, HO;Bergkvist, L;Magnusson, C;Persson, I;Chang-Claude, J;Paul, C;Skegg, DCG;Spears, GFS;Boyle, P;Evstifeeva, T;Daling, JR;Hutchinson, WB;Malone, K;Noonan, EA;Stanford, JL;Thomas, DB;Weiss, NS;White, E;Andrieu, N;Brêmond, A;Clavel, F;Gairard, B;Lansac, J;Piana, L;Renaud, R;Izquierdo, A;Viladiu, P;Cuevas, HR;Ontiveros, P;Palet, A;Salazar, SB;Arsitizabal, N;Cuadros, A;Tryggvadottir, L;Tulinius, H;Bachelot, A;Lê, MG;Peto, J;Franceschi, S;Lubin, F;Modan, B;Ron, E;Wax, Y;Friedman, GD;Hiatt, RA;Levi, F;Bishop, T;Kosmelj, K;Primic-Zakelj, M;Ravnihar, B;Stare, J;Beeson, WL;Fraser, G;Bulbrook, RD;Cuzick, J;Duffy, SW;Fentiman, IS;Hayward, JL;Wang, DY;McMichael, AJ;McPherson, K;Hanson, RL;Leske, MC;Mahoney, MC;Nasca, PC;Varma, AO;Weinstein, AL;Moller, TR;Olsson, H;Ranstam, J;Goldbohm, RA;van den Brandt, PA;Apelo, RA;Baens, J;de la Cruz, JR;Javier, B;Lacaya, LB;Ngelangel, CA;La Vecchia, C;Negri, E;Marubini, E;Ferraroni, M;Gerber, M;Richardson, S;Segala, C;Gatei, D;Kenya, P;Kungu, A;Mati, JG;Brinton, LA;Hoover, R;Schairer, C;Spirtas, R;Lee, HP;Rookus, MA;van Leeuwen, FE;Schoenberg, JA;McCredie, M;Gammon, MD;Clarke, EA;Jones, L;Neil, A;Vessey, M;Yeates, D;Appleby, P;Banks, E;Bull, D;Crossley, B;Goodill, A;Green, J;Hermon, C;Key, T;Langston, N;Lewis, C;Reeves, G;Collins, R;Doll, R;Peto, R;Mabuchi, K;Preston, D;Hannaford, P;Kay, C;Rosero-Bixby, L;Gao, YT;Jin, F;Yuan, JM;Wei, HY;Yun, T;Zhiheng, C;Berry, G;Cooper Booth, J;Jelihovsky, T;MacLennan, R;Shearman, R;Wang, QS;Baines, CJ;Miller, AB;Wall, C;Lund, E;Stalsberg, H;Shu, XO;Zheng, W;Katsouyanni, K;Trichopoulou, A;Trichopoulos, D;Dabancens, A;Martinez, L;Molina, R;Salas, O;Alexander, XE;Anderson, K;Folsom, AR;Hulka, BS;Bernstein, L;Enger, S;Haile, RW;Paganini-Hill, A;Pike, MC;Ross, RK;Ursin, G;Yu, MC;Longnecker, MP;Newcomb, P;Bergkvist, L;Kalache, A;Farley, TMM;Holck, S;Meirik, O
通讯作者：
Meirik, O
影响因子：
8.8
作者：
Julka, P. K.;Chacko, R. T.;Nag, S.;Parshad, R.;Nair, A.;Oh, D. S.;Hu, Z.;Koppiker, C. B.;Nair, S.;Dawar, R.;Dhindsa, N.;Miller, I. D.;Ma, D.;Lin, B.;Awasthy, B.;Perou, C. M.
通讯作者：
Perou, C. M.
DOI：
10.1097/01.alc.0000130812.85638.e1
发表时间：
2004-07-01
影响因子：
3.2
作者：
Petri, AL;Tjonneland, A;Gronbæk, M
通讯作者：
Gronbæk, M
DOI：
10.1111/j.1530-0277.2011.01654.x
发表时间：
2012-04-01
影响因子：
3.2
作者：
Wong, Amy W.;Dunlap, Sarah M.;Nunez, Nomeli P.
通讯作者：
Nunez, Nomeli P.
影响因子：
6.4
作者：
Suzuki, Reiko;Orsini, Nicola;Wolk, Alicja
通讯作者：
Wolk, Alicja