Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy.

Tan TT; Degenhardt K; Nelson DA; Beaudoin B; Nieves Neira W; Bouillet P; Villunger A; Adams JM; White E

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Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy.

机译：BIM驱动的凋亡在上皮肿瘤和合理化疗中的关键作用。

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Defective apoptosis not only promotes tumorigenesis, but also can confound chemotherapeutic response. Here we demonstrate that the proapoptotic BH3-only protein BIM is a tumor suppressor in epithelial solid tumors and also is a determinant in paclitaxel sensitivity in vivo. Furthermore, the H-ras/mitogen-activated protein kinase (MAPK) pathway conferred resistance to paclitaxel that was dependent on functional inactivation of BIM. Whereas paclitaxel induced BIM accumulation and BIM-dependent apoptosis in vitro and in tumors in vivo, the H-ras/MAPK pathway suppressed this BIM induction by phosphorylating BIM and targeting BIM for degradation in proteasomes. The proteasome inhibitor Velcade (P-341, Bortezomib) restored BIM induction, abrogated H-ras-dependent paclitaxel resistance, and promoted BIM-dependent tumor regression, suggesting the potential benefits of combinatorial chemotherapy of Velcade and paclitaxel.

机译：有缺陷的凋亡不仅促进肿瘤发生，而且还会混淆化学疗法的反应。在这里，我们证明了仅凋亡的BH3蛋白BIM是上皮实体瘤中的肿瘤抑制因子，也是体内紫杉醇敏感性的决定因素。此外，H-ras /丝裂原激活的蛋白激酶（MAPK）通路赋予了对紫杉醇的抗药性，这取决于BIM的功能失活。紫杉醇在体外和体内肿瘤诱导BIM积累和BIM依赖性细胞凋亡，而H-ras / MAPK途径通过磷酸化BIM并靶向BIM降解蛋白酶体来抑制BIM诱导。蛋白酶体抑制剂Velcade（P-341，Bortezomib）恢复了BIM诱导，废除了H-ras依赖性紫杉醇耐药性，并促进了BIM依赖性肿瘤消退，表明Velcade和紫杉醇联合化疗的潜在益处。

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《Cancer Cell》 |2005年第3期|共12页
作者
Tan TT; Degenhardt K; Nelson DA; Beaudoin B; Nieves Neira W; Bouillet P; Villunger A; Adams JM; White E;
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正文语种 eng
中图分类肿瘤学;
关键词
Antineoplastic Agents; Phytogenic; Apoptosis; Carrier Proteins; Membrane Proteins; 抗肿瘤药; 植物; 脱噬作用; 载体蛋白质类; 膜蛋白质类; 肿瘤; 腺和上皮; 紫杉酚;

机译：Antineoplastic Agents;Phytogenic;Apoptosis;Carrier Proteins;Membrane Proteins;抗肿瘤药;植物;脱噬作用;载体蛋白质类;膜蛋白质类;肿瘤;腺和上皮;紫杉酚;

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1. Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy. [J] . Tan TT, Degenhardt K, Nelson DA, Cancer Cell . 2005,第3期

机译：BIM驱动的凋亡在上皮肿瘤和合理化疗中的关键作用。
2. LncSOX4 serves an oncogenic role in the tumorigenesis of epithelial ovarian cancer by promoting cell proliferation and inhibiting apoptosis [J] . Liu Yulan, Wang Yan, Yao Dongmei, Molecular medicine reports . 2018,第6aPta2期

机译：LNCSOX4通过促进细胞增殖和抑制细胞凋亡，在上皮性卵巢癌的肿瘤瘤中发挥致癌作用
3. COX-2 and survivin reduction may play a role in berberine-induced apoptosis in human ductal breast epithelial tumor cell line. [J] . Pazhang Y, Ahmadian S, Javadifar N, Tumour biology : . 2012,第1期

机译：COX-2和survivin的减少可能在小ber碱诱导的人导管乳腺上皮肿瘤细胞系的凋亡中起作用。
4. human Chorionic Gonadotropin and Deriveted-Angiotensin Peptides Effects on Cell Viability and on Apoptosis in Tumoral (MCF-7) and in Normal (MCF10A) Epithelial Breast Cells [C] . Alves Correa-Noronha S.A., Ribeiro de Noronha S.M., Shimuta S.I., International Congress on Cell Biology. . 2013

机译：人绒毛膜促性腺激素和衍生血管紧张素肽对细胞活力和肿瘤（MCF-7）和正常（MCF10A）上皮乳腺细胞的影响
5. Role of Bcl-2 proteins in stress-induced apoptosis in a non-transformed mammary epithelial cell line. [D] . Butler, Kristie Lynn. 2014

机译：Bcl-2蛋白在非转化乳腺上皮细胞系中在应激诱导的细胞凋亡中的作用。
6. Finding a New Role for NEMO: A Key Player in Preventing Hepatocyte Apoptosis and Liver Tumorigenesis by Inhibiting RIPK1 [O] . I-Fang Hsin, Erica Montano, Ekihiro Seki -1

机译：寻找NEMO的新角色：通过抑制RIPK1预防肝细胞凋亡和肝肿瘤发生的关键因素
7. Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy [O] . Tan Ting-Ting, Degenhardt Kurt, Nelson Deirdre A., 2005

机译：BIM驱动的凋亡在上皮肿瘤中的关键作用和合理的化学疗法

Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy.

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