Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front

Cloud P. Pjaweletz, Lu Charboneau, Verena E. Bichsel, Nicole L. Simone, Tina Chen, John W. Gillespie, Michael R. Emmert-Buck, Mark J. Roth, Emanuel F. Petricoin, Lance A. Liotta*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

856 Scopus citations

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.

Original languageEnglish
Pages (from-to)1981-1989
Number of pages9
JournalOncogene
Volume20
Issue number16
DOIs
StatePublished - 12 Apr 2001
Externally publishedYes

Keywords

  • Akt
  • Apoptosis
  • Laser capture microdissection
  • Mitogen activated protein kinase
  • Protein microarrays
  • Tumor progression

Fingerprint

Dive into the research topics of 'Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front'. Together they form a unique fingerprint.

Cite this