| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Imaging, Diagnosis, Prognosis |
Authors' Affiliations: 1 Arizona Cancer Center, University of Arizona, Tucson, Arizona and 2 Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio
Requests for reprints: Garth Powis, Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson AZ 85724. Phone: 520-626-6408; Fax: 520-626-4848; E-mail: gpowis{at}azcc.arizona.edu.
Purpose: The purpose of the study was to evaluate the stability of phosphoprotein as a marker of signaling activity in human tumors using clinical samples and xenografts.
Experimental Design: The expression of phospho-Ser473-Akt (p-Akt) was assessed by immunohistochemistry in paraffin-embedded samples from patients enrolled in a Southwest Oncology Group clinical trial of gastroesophageal junction tumors and by immunohistochemistry and Western blotting in human colon tumor xenografts at various times after removal from the animal.
Results: Clinical samples had evaluable p-Akt staining only when obtained as biopsies (9 of 13) and no staining was observed in tumors obtained as surgically resected samples (0 of 15). In HT-29 colon cancer xenografts, p-Akt staining was present in fresh sample but not in tissue that had been allowed to stand for 30 minutes at room temperature. Western blotting of HT-29 tumor xenografts at room temperature showed a slow decrease in total Akt with a half-life of 180 minutes and a rapid decrease in p-Akt with a half-life of 20 minutes.
Conclusions: Caution should be used when using phosphoprotein levels in human tumor specimens to measure intrinsic signaling activity or drug effects because of the potential for rapid dephosphorylation. Rapid processing of biopsies is essential and postoperative surgical samples may be of limited value because of the time to fixation.
Key Words: phosphatidylinositol-3-kinase • Akt • phospho-Akt • tumor • stability
This article has been cited by other articles:
|
|
 |
|
  J. H. Doroshow and R. E. Parchment Oncologic Phase 0 Trials Incorporating Clinical Pharmacodynamics: from Concept to Patient Clin. Cancer Res., June 15, 2008; 14(12): 3658 - 3663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Taillade, F Penault-Llorca, T Boulet, P Fouret, S Michiels, E Taranchon, G Mountzios, P Validire, J Domont, P Girard, et al. Immunohistochemichal expression of biomarkers: a comparative study between diagnostic bronchial biopsies and surgical specimens of non-small-cell lung cancer Ann. Onc., June 1, 2007; 18(6): 1043 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Dragovich and C. Fenoglio-Preiser In Reply J. Clin. Oncol., March 1, 2007; 25(7): 911 - 911. [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Han, T.-Y. Kim, Y. K. Jeon, P. G. Hwang, S.-A. Im, K.-H. Lee, J. H. Kim, D.-W. Kim, D. S. Heo, N. K. Kim, et al. Optimization of Patient Selection for Gefitinib in Non-Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation Clin. Cancer Res., April 15, 2006; 12(8): 2538 - 2544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Rothenberg, B. LaFleur, D. E. Levy, M. K. Washington, S. L. Morgan-Meadows, R. K. Ramanathan, J. D. Berlin, A. B. Benson III, and R. J. Coffey Randomized Phase II Trial of the Clinical and Biological Effects of Two Dose Levels of Gefitinib in Patients With Recurrent Colorectal Adenocarcinoma J. Clin. Oncol., December 20, 2005; 23(36): 9265 - 9274. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
