Alteration of BRCA1 expression affects alcohol-induced transcription of RNA Pol III-dependent genes.
Alteration of BRCA1 expression affects alcohol-induced transcription of RNA Pol III-dependent genes.
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DOI：
10.1016/j.gene.2014.11.009
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发表时间：
2015-02-01
期刊：
影响因子：
3.5
通讯作者：
Zhong S
中科院分区：
文献类型：
--
作者：
Zhong Q;Shi G;Zhang Y;Lu L;Levy D;Zhong S
新出现的证据表明，饮酒是乳腺癌的一个既定危险因素。RNA聚合酶III（Pol III）转录的失调增强细胞Pol III基因的产生，导致翻译能力的增加以促进细胞转化和肿瘤形成。我们已经报道了酒精摄入增加Pol III基因转录，促进体外和体内细胞转化和肿瘤形成。研究表明，肿瘤抑制因子pRb、p53、PTEN和Maf 1抑制Pol III基因的转录。BRCA 1是一种肿瘤抑制因子，其突变与乳腺癌的发生密切相关。然而，目前尚不清楚BRCA 1的表达是否影响酒精诱导的Pol III基因的转录。在目前的研究中，我们报告说，在肝癌1937细胞，这是一个BRCA 1缺陷的细胞系，恢复BRCA 1，抑制Pol III基因转录。在这些细胞中表达突变或截短的BRCA 1不影响对Pol III基因的阻遏能力。我们的分析表明，酒精诱导Pol III基因转录。更重要的是，BRCA 1在雌激素受体阳性（ER+）乳腺癌细胞（MCF-7）中的过表达减少了酒精对tRNALeu和5S rRNA基因的诱导，而BRCA 1的siRNA减少了这类基因的转录。这表明BRCA 1与酒精诱导的Pol III基因失调有关。这些研究首次证明了BRCA 1在酒精诱导Pol III基因中的作用，并揭示了酒精相关乳腺癌的新机制。
Emerging evidence has indicated that alcohol consumption is an established risk factor for breast cancer. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular Pol III gene production, leading to an increase in translational capacity to promote cell transformation and tumor formation. We have reported that alcohol intake increases Pol III gene transcription to promote cell transformation and tumor formation in vitro and in vivo. Studies revealed that tumor suppressors, pRb, p53, PTEN and Maf1 repress the transcription of Pol III genes. BRCA1 is a tumor suppressor and its mutation is tightly related to breast cancer development. However, it is not clear whether BRCA1 expression affects alcohol-induced transcription of Pol III genes. At the present studies, we report that restoring BRCA1 in HCC 1937 cells, which is a BRCA1 deficient cell line, represses Pol III gene transcription. Expressing mutant or truncated BRCA1 in these cells does not affect the ability of repression on Pol III genes. Our analysis has demonstrated that alcohol induces Pol III gene transcription. More importantly, overexpression of BRCA1 in estrogen receptor positive (ER+) breast cancer cells (MCF-7) decreases the induction of tRNALeu and 5S rRNA genes by alcohol, whereas reduction of BRCA1 by its siRNA slightly increases the transcription of the class of genes. This suggests that BRCA1 is associated with alcohol-induced deregulation of Pol III genes. These studies for the first time demonstrate the role of BRCA1 in induction of Pol III genes by alcohol and uncover a novel mechanism of alcohol-associated breast cancer.
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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
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：
6.4
作者：
Suzuki, Reiko;Orsini, Nicola;Wolk, Alicja
通讯作者：
Wolk, Alicja
影响因子：
3.8
作者：
Friedenson B
通讯作者：
Friedenson B
影响因子：
8
作者：
Marks, JR;Huper, G;Iglehart, JD
通讯作者：
Iglehart, JD