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

Oncogene volume 20, pages 1981–1989 (2001)Cite this article

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.

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Acknowledgements

We thank Dr Phil R Taylor of the Cancer Prevention Studies Branch, National Cancer Institute, Bethesda, Maryland, USA, and Drs Quan-Hong Wang, Wen-Jie Guo and Yong-Zhen Zhang of the Shanxi Cancer Hospital and Institute, Taiyuan, Shanxi, China for coordinating and conducting all the field related and tissue procurement activities in China.

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Authors and Affiliations

  1. Division of Therapeutic Proteins, Tissue Proteomics Unit, CBER, Food and Drug Administration, Bethesda, MD 20892, Maryland, USA

    Cloud P Paweletz, Verena E Bichsel & Emanuel F Petricoin III

  2. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, Maryland, USA

    Cloud P Paweletz, Lu Charboneau, Verena E Bichsel, Nicole L Simone, Tina Chen & Lance A Liotta

  3. Department of Chemistry, Georgetown University, Washington, 20057, District of Columbia, DC, USA

    Cloud P Paweletz

  4. Cancer Genome Anatomy Project, Office of the Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland MD 20892, USA

    John W Gillespie

  5. Pathogenetics Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, Maryland, USA

    Michael R Emmert-Buck

  6. Cancer Prevention Studies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, Maryland, USA

    Mark J Roth

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  1. Cloud P Paweletz
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  2. Lu Charboneau
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Paweletz, C., Charboneau, L., Bichsel, V. et al. Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front. Oncogene 20, 1981–1989 (2001). https://doi.org/10.1038/sj.onc.1204265

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  • DOI: https://doi.org/10.1038/sj.onc.1204265

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