BAD-mediated apoptotic pathway is associated with human cancer development.
BAD-mediated apoptotic pathway is associated with human cancer development.
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坏介导的凋亡途径与人类癌症的发展有关。
DOI：
10.3892/ijmm.2015.2091
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发表时间：
2015-04
影响因子：
5.4
通讯作者：
Lancaster JM
中科院分区：
文献类型：
--
作者：
Stickles XB;Marchion DC;Bicaku E;Al Sawah E;Abbasi F;Xiong Y;Bou Zgheib N;Boac BM;Orr BC;Judson PL;Berry A;Hakam A;Wenham RM;Apte SM;Berglund AE;Lancaster JM
正常细胞的恶性转化部分是由异常基因表达破坏细胞增殖、凋亡、衰老和DNA修复的调节引起的。有证据表明，Bcl-2拮抗剂细胞死亡（BAD）介导的凋亡途径影响癌症的化疗耐药性。在本研究中，我们探讨了BAD介导的凋亡途径在癌症发展和进展中的作用。使用主成分分析来获得代表通路表达的数值分数，我们评估了来自不同类型的相应正常、浸润前和浸润性癌症（例如卵巢癌、子宫内膜癌、乳腺癌和结肠癌）的临床基因组数据集（n = 427），以确定BAD介导的凋亡通路与癌症发展之间的关联。免疫荧光法用于比较磷酸化BAD [pBAD（丝氨酸-112，-136和-155）]在永生化的正常和侵袭性卵巢癌，结肠癌和乳腺癌细胞中的表达水平。通过RT-qPCR评估正常和卵巢癌组织样品中BAD介导的凋亡途径磷酸酶PP2C的表达。pBAD蛋白水平在永生化的正常细胞和癌细胞中的生长促进作用使用MTS测定的siRNA消耗实验来评估。BAD介导的凋亡通路的表达与卵巢癌的发生和/或进展有关，（n = 106，p <0.001），乳腺（n = 185，p <0.0008; n = 61，p = 0.04），结肠癌（n = 22，p <0.001）和子宫内膜癌（n = 33，p <0.001），以及卵巢子宫内膜异位症（n = 20，p <0.001）。与永生化正常细胞相比，在癌细胞中观察到更高的pBAD蛋白水平，而与卵巢肿瘤组织样品相比，PP2C基因表达在癌症中较低（n = 76，p <0.001）。PP2C耗竭后增加的pBAD蛋白水平赋予永生化的正常细胞和癌细胞生长优势。因此，BAD介导的凋亡途径与可能受pBAD蛋白水平影响的人类癌症的发展相关。
The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistance. In the present study, we explored the role of the BAD-mediated apoptotic pathway in the development and progression of cancer. Using principal component analysis to derive a numeric score representing pathway expression, we evaluated clinico-genomic datasets (n=427) from corresponding normal, pre-invasive and invasive cancers of different types, such as ovarian, endometrial, breast and colon cancers in order to determine the associations between the BAD-mediated apoptotic pathway and cancer development. Immunofluorescence was used to compare the expression levels of phosphorylated BAD [pBAD (serine-112, -136 and -155)] in immortalized normal and invasive ovarian, colon and breast cancer cells. The expression of the BAD-mediated apoptotic pathway phosphatase, PP2C, was evaluated by RT-qPCR in the normal and ovarian cancer tissue samples. The growth-promoting effects of pBAD protein levels in the immortalized normal and cancer cells were assessed using siRNA depletion experiments with MTS assays. The expression of the BAD-mediated apoptotic pathway was associated with the development and/or progression of ovarian (n=106, p<0.001), breast (n=185, p<0.0008; n=61, p=0.04), colon (n=22, p<0.001) and endometrial (n=33, p<0.001) cancers, as well as with ovarian endometriosis (n=20, p<0.001). Higher pBAD protein levels were observed in the cancer cells compared to the immortalized normal cells, whereas PP2C gene expression was lower in the cancer compared to the ovarian tumor tissue samples (n=76, p<0.001). The increased pBAD protein levels after the depletion of PP2C conferred a growth advantage to the immortalized normal and cancer cells. The BAD-mediated apoptotic pathway is thus associated with the development of human cancers likely influenced by the protein levels of pBAD.
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影响因子：
4.1
作者：
Lizcano, JM;Morrice, N;Cohen, P
通讯作者：
Cohen, P
影响因子：
3.9
作者：
Bansal N;Marchion DC;Bicaku E;Xiong Y;Chen N;Stickles XB;Sawah EA;Wenham RM;Apte SM;Gonzalez-Bosquet J;Judson PL;Hakam A;Lancaster JM
通讯作者：
Lancaster JM
DOI：
10.1158/1078-0432.ccr-11-0735
发表时间：
2011-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Marchion DC;Cottrill HM;Xiong Y;Chen N;Bicaku E;Fulp WJ;Bansal N;Chon HS;Stickles XB;Kamath SG;Hakam A;Li L;Su D;Moreno C;Judson PL;Berchuck A;Wenham RM;Apte SM;Gonzalez-Bosquet J;Bloom GC;Eschrich SA;Sebti S;Chen DT;Lancaster JM
通讯作者：
Lancaster JM
影响因子：
64.5
作者：
YANG, E;ZHA, JP;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ
影响因子：
4.2
作者：
Klumpp, S;Selke, D;Krieglstein, J
通讯作者：
Krieglstein, J