Alcohol promotes breast cancer cell invasion by regulating the Nm23-ITGA5 pathway.
Alcohol promotes breast cancer cell invasion by regulating the Nm23-ITGA5 pathway.
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DOI：
10.1186/1756-9966-30-75
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发表时间：
2011-08-12
期刊：
影响因子：
--
通讯作者：
Nunez NP
中科院分区：
文献类型：
--
作者：
Wong AW;Paulson QX;Hong J;Stubbins RE;Poh K;Schrader E;Nunez NP
饮酒是乳腺癌转移的既定危险因素。然而，酒精促进乳腺癌转移的机制尚不清楚。癌细胞侵入组织屏障（例如基底膜和间质）的能力是建立癌症转移的重要步骤。在本研究中，我们鉴定并检查了两个基因 Nm23 和 ITGA5 在酒精诱导的乳腺癌细胞侵袭中的作用。用不同浓度的乙醇处理人乳腺癌T47D细胞。博伊登室侵袭测定用于测量细胞侵袭能力。通过qRT-PCR测定包括Nm23在内的转移抑制基因的mRNA表达水平。 ITGA5 是通过 qRT-PCR 阵列鉴定的，该阵列包含 84 个对于细胞-细胞和细胞-细胞外基质相互作用很重要的基因。除了 Nm23 和 ITGA5 敲低之外，还使用 Nm23 过表达来确定 Nm23-ITGA5 途径对 T47D 细胞的细胞侵袭能力的作用。通过蛋白质印迹验证蛋白质表达水平。酒精通过抑制 Nm23 转移抑制基因，以剂量依赖性方式增加人乳腺癌 T47D 细胞的侵袭能力。反过来，Nm23 下调会增加纤连蛋白受体亚基 ITGA5 的表达，从而导致细胞侵袭增加。此外，Nm23 过表达可有效抑制酒精对细胞侵袭的影响。此外，我们发现，ITGA5 的敲低也抑制了酒精对侵袭的影响。我们的结果表明，Nm23-ITGA5 通路在酒精诱导的乳腺癌细胞侵袭中发挥着关键作用。因此，对该途径的调节可能可用于预防人类乳腺癌中酒精促进的转移的形成。
Alcohol consumption is an established risk factor for breast cancer metastasis. Yet, the mechanism by which alcohol promotes breast cancer metastases is unknown. The ability of cancer cells to invade through tissue barriers (such as basement membrane and interstitial stroma) is an essential step towards establishing cancer metastasis. In the present study, we identify and examine the roles of two genes, Nm23 and ITGA5, in alcohol-induced breast cancer cell invasion. Human breast cancer T47D cells were treated with ethanol at various concentrations. Boyden chamber invasion assays were used to measure cellular invasive ability. The mRNA expression level of metastasis suppressor genes including Nm23 was determined by qRT-PCR. ITGA5 was identified using a qRT-PCR array of 84 genes important for cell-cell and cell-extracellular matrix interactions. Nm23 overexpression in addition to Nm23- and ITGA5 knock-down were used to determine the role of the Nm23-ITGA5 pathway on cellular invasive ability of T47D cells. Protein expression levels were verified by Western blot. Alcohol increased the invasive ability of human breast cancer T47D cells in a dose-dependent manner through the suppression of the Nm23 metastatic suppressor gene. In turn, Nm23 down-regulation increased expression of fibronectin receptor subunit ITGA5, which subsequently led to increased cellular invasion. Moreover, Nm23 overexpression was effective in suppressing the effects of alcohol on cell invasion. In addition, we show that the effects of alcohol on invasion were also inhibited by knock-down of ITGA5. Our results suggest that the Nm23-ITGA5 pathway plays a critical role in alcohol-induced breast cancer cell invasion. Thus, regulation of this pathway may potentially be used to prevent the establishment of alcohol-promoted metastases in human breast cancers.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
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
DOI：
10.1038/nrc2594
发表时间：
2009-04
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.7
作者：
Lee, HY;Lee, H
通讯作者：
Lee, H
影响因子：
3.6
作者：
Qin, L;Wang, YL;Piao, YS
通讯作者：
Piao, YS