Different changes in protein and phosphoprotein levels result from serum starvation of high-grade glioma and adenocarcinoma cell lines.
Different changes in protein and phosphoprotein levels result from serum starvation of high-grade glioma and adenocarcinoma cell lines.
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DOI：
10.1021/pr900392b
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发表时间：
2010-01
影响因子：
4.4
通讯作者：
Baggerly, Keith A.
中科院分区：
文献类型：
--
作者：
Levin, Victor A.;Panchabhai, Sonali C.;Shen, Li;Kornblau, Steven M.;Qiu, Yihua;Baggerly, Keith A.
在体外经历血清饥饿的肿瘤细胞部分地模拟代谢应激细胞，其试图通过诱导信号转导和基因表达来适应体内变化的环境，使得肿瘤继续生长。我们的假设是血清饥饿后蛋白质和磷蛋白水平的变化可能反映了肿瘤的适应表型，这可能是治疗的靶点。我们使用反相蛋白质微阵列询问5个高级别胶质瘤细胞系和7个腺癌细胞系的81种蛋白质和25种磷蛋白水平的差异。所有细胞系均在10%FBS的良好补料生长条件和0.5%FBS的饥饿条件下进行研究。将蛋白质表达水平标准化为β-肌动蛋白，并将其分为增加（+1，上第75个四分位数）、减少（-1，最低第25个四分位数）或不变（0，其他），以关注蛋白质和磷蛋白水平的最大（希望是最稳健的）变化模式。我们检查了这些饥饿值，以更好地理解细胞系之间的饥饿-进食差异，从而更好/更清楚地了解血清饥饿对潜在细胞反应的影响。在一般情况下，FBS饥饿后24小时的蛋白质和磷蛋白的表达增加更经常在胶质瘤细胞系比腺癌细胞系，这似乎有较少的增加蛋白质的分数和更多的分数下降。胶质瘤中增加的许多蛋白质是PTEN-PI-3激酶-AKT、EGFR-MAPK-Stat和转录激活因子-多胺信号通路的下游靶点。在腺癌中，蛋白质和磷蛋白的表达通常在凋亡途径中增加，而在上述其他途径中有微小的波动。相反，胶质瘤在血清饥饿24小时后变得对细胞凋亡有抵抗力，并且比腺癌更能上调转录激活因子和多胺。
Tumor cells undergoing serum starvation in vitro partially mimic metabolically stressed cells trying to adjust to a changed environment in vivo by inducing signal transduction and gene expression so that the tumor continues to grow. Our hypothesis is that the changes in protein and phosphoprotein levels after serum starvation may reflect the adapted phenotype of the tumor, which could be targeted for therapy. We used reverse-phase protein microarrays to interrogate five high-grade glioma cell lines and seven adenocarcinoma cell lines for differences in the level of 81 proteins and 25 phosphoproteins. All cell lines were studied in the well-fed condition of growth with 10% FBS and the starved condition of 0.5% FBS. Protein expression levels were normalized to β-actin and trichotomized as increased (+1, upper 75th quartile), decreased (−1, lowest 25th quartile), or unchanged (0, others) to focus on the patterns of the biggest (and hopefully most robust) changes in protein and phosphoprotein levels. We examined these trichotomized values to better understand Starved-Fed differences among the cell lines and thereby gain better/clearer insight into the effects of serum starvation on potential cellular responses. In general, the expression of proteins and phosphoproteins 24 h after FBS starvation increased more often in glioma lines than in adenocarcinoma lines, which appeared to have fewer increased protein scores and more decreased scores. Many of the proteins increased in gliomas were downstream targets of the PTEN-PI-3 kinase-AKT, EGFR-MAPK-Stat, and transcription activator-polyamine signaling pathways. In adenocarcinomas, the expression of proteins and phosphoproteins generally increased in apoptosis pathways, while there were minor fluctuations in the other pathways above. Contrawise, gliomas become resistant to apoptosis after 24 h of serum starvation and upregulate transcription activators and polyamines more so than adenocarciomas.
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DOI：
10.1073/pnas.232087499
发表时间：
2002-11-12
影响因子：
11.1
作者：
Sakakibara, S;Nakamura, Y;Okano, H
通讯作者：
Okano, H
影响因子：
20.3
作者：
Alsina, M;Fonseca, R;Sebti, SM
通讯作者：
Sebti, SM
影响因子：
4.8
作者：
Luo, WB;Wang, YF;Reiser, G
通讯作者：
Reiser, G
影响因子：
2.8
作者：
Kajiwara, Yoshinori;Panchabhai, Sonali;Levin, Victor A.
通讯作者：
Levin, Victor A.
影响因子：
2.8
作者：
Kajiwara, Yoshinori;Panchabhai, Sonali;Levin, Victor A.
通讯作者：
Levin, Victor A.