Protein-based identification of quantitative trait loci associated with malignant transformation in two HER2+ cellular models of breast cancer.
Protein-based identification of quantitative trait loci associated with malignant transformation in two HER2+ cellular models of breast cancer.
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DOI：
10.1186/1477-5956-10-11
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发表时间：
2012-02-22
期刊：
影响因子：
2
通讯作者：
Klinke DJ 2nd
中科院分区：
文献类型：
--
作者：
Kulkarni YM;Klinke DJ 2nd
现代对癌症基因组的看法揭示了与正常细胞相比广泛的重排。然而，这些基因改变如何转化为特定的蛋白质组变化，从而支持获得癌症特征，这一问题仍然悬而未决。本研究的目的是量化两种乳腺癌 HER2+ 细胞模型中蛋白质表达的变化，并推断这些模型中与癌症标志相关的差异调节信号通路。使用蛋白质组工作流程来鉴定两种 HER2 阳性致瘤细胞系（BT474 和 SKBR3）中相对于正常人乳腺上皮细胞系 (184A1) 差异表达的蛋白质。总共鉴定出 64 个 (BT474-184A1) 和 69 个 (SKBR3-184A1) 蛋白质，其差异表达至少为 1.5 倍。使用通路推断工具根据肿瘤细胞系中功能丰富的通路来解释这些蛋白质。我们观察到“蛋白质泛素化”和“细胞凋亡信号”途径在两种乳腺癌模型中均富集，而“IGF信号”和“细胞运动”途径在BT474中富集，“氨基酸代谢”在SKBR3细胞系中富集。虽然“蛋白质泛素化”和“细胞凋亡信号传导”途径对于两种细胞系来说是共同的，但观察到的蛋白质表达模式表明，每种致瘤细胞系中的细胞凋亡逃避是通过不同的机制发生的。显然，与184A1相比，BT474中的细胞凋亡是通过Bid的下调来调节的，而SKBR3中的细胞凋亡是通过Calpain-11的上调来调节的。
A contemporary view of the cancer genome reveals extensive rearrangement compared to normal cells. Yet how these genetic alterations translate into specific proteomic changes that underpin acquiring the hallmarks of cancer remains unresolved. The objectives of this study were to quantify alterations in protein expression in two HER2+ cellular models of breast cancer and to infer differentially regulated signaling pathways in these models associated with the hallmarks of cancer. A proteomic workflow was used to identify proteins in two HER2 positive tumorigenic cell lines (BT474 and SKBR3) that were differentially expressed relative to a normal human mammary epithelial cell line (184A1). A total of 64 (BT474-184A1) and 69 (SKBR3-184A1) proteins were uniquely identified that were differentially expressed by at least 1.5-fold. Pathway inference tools were used to interpret these proteins in terms of functionally enriched pathways in the tumor cell lines. We observed "protein ubiquitination" and "apoptosis signaling" pathways were both enriched in the two breast cancer models while "IGF signaling" and "cell motility" pathways were enriched in BT474 and "amino acid metabolism" were enriched in the SKBR3 cell line. While "protein ubiquitination" and "apoptosis signaling" pathways were common to both the cell lines, the observed patterns of protein expression suggest that the evasion of apoptosis in each tumorigenic cell line occurs via different mechanisms. Evidently, apoptosis is regulated in BT474 via down regulation of Bid and in SKBR3 via up regulation of Calpain-11 as compared to 184A1.
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影响因子：
64.5
作者：
Cox, Juergen;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
14.9
作者：
Huang DW;Sherman BT;Tan Q;Kir J;Liu D;Bryant D;Guo Y;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.2
作者：
Amm, Hope M.;Zhou, Tong;Buchsbaum, Donald J.
通讯作者：
Buchsbaum, Donald J.