Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens

被引：90

作者：

Fan, Alice C. ^{[1
,2
]}

Deb-Basu, Debabrita ^{[3
]}

Orban, Mathias W. ^{[1
,2
]}

Gotlib, Jason R. ^{[4
]}

Natkunam, Yasodha

O'Neill, Roger ^{[3
]}

Padua, Rose-Ann ^{[5
]}

Xu, Liwen ^{[1
,2
]}

Taketa, Daryl ^{[3
]}

Shirer, Amy E. ^{[1
,2
]}

Beer, Shelly ^{[1
,2
]}

Yee, Ada X. ^{[1
,2
]}

Voehringer, David W. ^{[3
]}

Felsher, Dean W. ^{[1
,2
]}

机构：

[1] Stanford Univ, Sch Med, Div Oncol, Dept Med, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Div Oncol, Dept Pathol, Stanford, CA 94305 USA

[3] Cell Biosci, Palo Alto, CA USA

[4] Stanford Univ, Sch Med, Div Hematol, Stanford Canc Ctr,Dept Med, Stanford, CA 94305 USA

[5] Hop St Louis, INSERM, Inst Univ Hematol, U718, Paris, France

来源：

NATURE MEDICINE | 2009年 / 15卷 / 05期

关键词：

HUMAN FOLLICULAR LYMPHOMA; CHRONIC MYELOID-LEUKEMIA; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; C-MYC ONCOGENE; BCR-ABL; PROTEIN EXPRESSION; PROGNOSTIC-SIGNIFICANCE; BCL-2; GENE; K562; CELLS;

D O I：

10.1038/nm.1903

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Current methods of protein detection are insensitive to detecting subtle changes in oncoprotein activation that underlie key cancer signaling processes. The requirement for large numbers of cells precludes serial tumor sampling for assessing a response to therapeutics. Therefore, we have developed a nanofluidic proteomic immunoassay (NIA) to quantify total and low-abundance protein isoforms in nanoliter volumes. Our method can quantify amounts of MYC oncoprotein and B cell lymphoma protein-2 (BCL2) in Burkitt's and follicular lymphoma; identify changes in activation of extracellular signal-related kinases-1 (ERK1) and ERK2, mitogen-activated kinase-1 (MEK), signal transducer and activator of transcription protein-3 (STAT3) and STAT5, c-Jun N-terminal kinase (JNK) and caspase-3 in imatinib-treated chronic myelogeneous leukemia (CML) cells; measure an unanticipated change in the phosphorylation of an ERK2 isomer in individuals with CML who responded to imatinib; and detect a decrease in STAT3 and STAT5 phosphorylation in individuals with lymphoma who were treated with atorvastatin. Therefore, we have described a new and highly sensitive method for determining oncoprotein expression and phosphorylation in clinical specimens for the development of new therapeutics for cancer.

引用

页码：566 / 571

页数：6

共 41 条

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Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma [J].