Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front
Top Cited Papers
- 12 April 2001
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 20 (16), 1981-1989
- https://doi.org/10.1038/sj.onc.1204265
Abstract
Protein arrays are described for screening of molecular markers and pathway targets in patient matched human tissue during disease progression. In contrast to previous protein arrays that immobilize the probe, our reverse phase protein array immobilizes the whole repertoire of patient proteins that represent the state of individual tissue cell populations undergoing disease transitions. A high degree of sensitivity, precision and linearity was achieved, making it possible to quantify the phosphorylated status of signal proteins in human tissue cell subpopulations. Using this novel protein microarray we have longitudinally analysed the state of pro-survival checkpoint proteins at the microscopic transition stage from patient matched histologically normal prostate epithelium to prostate intraepithelial neoplasia (PIN) and then to invasive prostate cancer. Cancer progression was associated with increased phosphorylation of Akt (P<0.04), suppression of apoptosis pathways (P<0.03), as well as decreased phosphorylation of ERK (P<0.01). At the transition from histologically normal epithelium to PIN we observed a statistically significant surge in phosphorylated Akt (P<0.03) and a concomitant suppression of downstream apoptosis pathways which proceeds the transition into invasive carcinoma.Keywords
This publication has 31 references indexed in Scilit:
- Increased AKT Activity Contributes to Prostate Cancer Progression by Dramatically Accelerating Prostate Tumor Growth and Diminishing p27Kip1 ExpressionOnline Journal of Public Health Informatics, 2000
- Substrate Specificity of αvβ3Integrin-mediated Cell Migration and Phosphatidylinositol 3-Kinase/AKT Pathway ActivationOnline Journal of Public Health Informatics, 2000
- Correlation of increased apoptosis and proliferation with development of prostatic intraepithelial neoplasia (PIN) in ventral prostate of the noble ratThe Prostate, 2000
- The Hallmarks of CancerCell, 2000
- High density synthetic oligonucleotide arraysNature Genetics, 1999
- Tissue microarrays for high-throughput molecular profiling of tumor specimensNature Medicine, 1998
- Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase BNature, 1995
- Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA MicroarrayScience, 1995
- Requirement for Phosphatidylinositol-3 Kinase in the Prevention of Apoptosis by Nerve Growth FactorScience, 1995
- Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activationCell, 1995