Journal article
Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma: Identification of RS/DJ-1 and RhoGDIα
Cancer research (Chicago, Ill.), Vol.63(20), pp.6928-6934
10/15/2003
PMID: 14583493
Abstract
The growing knowledge of the tight connection between apoptosis and cancer has lead to an explosion of research revolving around apoptotic induction with chemotherapeutic agents and small molecule inhibitors. The chemotherapeutic agent paclitaxel (Taxol) activates mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase and, combined with MEK inhibition, synergistically enhances apoptosis. Here we implement a proteomic approach using two-dimensional gels coupled with mass spectrometry to identify proteins altered with this coordinated combination treatment. We found that the combined treatment of paclitaxel and MEK inhibitor uniquely altered the proteins RS/DJ-1 (RNA-binding regulatory subunit/DJ-1 PARK7) and RhoGDIalpha (Rho GDP-dissociation inhibitor alpha). Functional proteomic analysis by exogenous expression or short interfering RNA targeting confirmed a role in survival and apoptosis for these proteins. Analysis of primary lung tumors with matched adjacent normal tissue confirmed RS/DJ-1 overexpression in non-small cell lung carcinoma. This study shows the power of proteomic profiling coupled with functional analysis for the discovery of novel molecular targets and potential cancer cell-specific biomarkers.
Details
- Title: Subtitle
- Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma: Identification of RS/DJ-1 and RhoGDIα
- Creators
- Jeffrey P Mackeigan - University of North Carolina at Chapel HillCasey M Clements - University of North Carolina at Chapel HillJohn D Lich - University of North Carolina at Chapel HillR. Marshall Pope - University of North Carolina at Chapel HillYaacov Hod - Prostate Cancer Research Center, Department of Urology, State University of New York, Stony Brook, New York 11794, United StatesJenny P-Y Ting - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.63(20), pp.6928-6934
- Publisher
- American Association for Cancer Research
- PMID
- 14583493
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 10/15/2003
- Academic Unit
- Medicine Administration
- Record Identifier
- 9984627299902771
Metrics
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