Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO My JCO Subscriptions Customer Service Site Map

Originally published as JCO Early Release 10.1200/JCO.2005.02.4133 on December 5 2005

Journal of Clinical Oncology, Vol 24, No 2 (January 10), 2006: pp. 306-314
© 2006 American Society of Clinical Oncology.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Right arrowRights & Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tsurutani, J.
Right arrow Articles by Dennis, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tsurutani, J.
Right arrow Articles by Dennis, P. A.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Evaluation of Two Phosphorylation Sites Improves the Prognostic Significance of Akt Activation in Non–Small-Cell Lung Cancer Tumors

Junji Tsurutani, Junya Fukuoka, Hiroko Tsurutani, Joanna H. Shih, Stephen M. Hewitt, William D. Travis, Jin Jen, Phillip A. Dennis

From the Cancer Therapeutics Branch; Laboratory of Population Genetics; Biometric Research Branch; and Laboratory of Pathology, National Cancer Institute, Bethesda, MD; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, DC

Address reprint requests to Phillip A. Dennis, MD, Building 8, Room 5101, 8901 Wisconsin Ave, Bethesda, MD 20889; e-mail: pdennis{at}nih.gov

PURPOSE: Akt is a serine/threonine kinase that has been implicated in lung tumorigenesis and lung cancer therapeutic resistance. Full activation of Akt requires two phosphorylation events, but only one site of phosphorylation (S473) has been evaluated thus far in clinical non–small-cell lung cancer (NSCLC) specimens, which has resulted in conflicting results regarding the prognostic significance of Akt activation in NSCLC. In this study, we sought to determine whether evaluation of Akt phosphorylation at T308 would improve prognostic accuracy.

PATIENTS AND METHODS: Phosphospecific antibodies against T308 and S473 were validated and used in an immunohistochemical analysis of tissue microarray slides containing NSCLC specimens (n = 300) and surrounding lung tissue specimens (n = 100).

RESULTS: Phosphorylation of either S473 or T308 was positive in most NSCSLC specimens, but was detected rarely in surrounding normal tissues. When Akt activation was defined by using both sites of phosphorylation, Akt activation was specific for NSCLC tumors versus surrounding tissue (73.4% v 0%; P < .05), was higher in adenocarcinoma than in squamous cell carcinoma (78.1% v 68.5%; P = .040), and was associated with shorter overall survival for all stages of disease (log-rank P = .041). In multivariate analyses, increased phosphorylation of T308 alone was a poor prognostic factor for stage I patients or for tumors < 5 cm (log-rank P = .011 and P = .015, respectively).

CONCLUSION: These results suggest that monitoring phosphorylation of Akt at T308 improves the assessment of Akt activation, and show that Akt activation is a poor prognostic factor for all stages of NSCLC.

Supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.

J.T. and J.F. contributed equally to this work.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
Ann OncolHome page
J.-C. Soria, F. A. Shepherd, J.-Y. Douillard, J. Wolf, G. Giaccone, L. Crino, F. Cappuzzo, S. Sharma, S. H. Gross, S. Dimitrijevic, et al.
Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors
Ann. Onc., October 1, 2009; 20(10): 1674 - 1681.
[Abstract] [Full Text] [PDF]


Home page
Anticancer ResHome page
S. AL-SAAD, T. DONNEM, K. AL-SHIBLI, M. PERSSON, R. M. BREMNES, and L.-T. BUSUND
Diverse Prognostic Roles of Akt Isoforms, PTEN and PI3K in Tumor Epithelial Cells and Stromal Compartment in Non-small Cell Lung Cancer
Anticancer Res, October 1, 2009; 29(10): 4175 - 4183.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
H. Ebi, S. Tomida, T. Takeuchi, C. Arima, T. Sato, T. Mitsudomi, Y. Yatabe, H. Osada, and T. Takahashi
Relationship of Deregulated Signaling Converging onto mTOR with Prognosis and Classification of Lung Adenocarcinoma Shown by Two Independent In silico Analyses
Cancer Res., May 1, 2009; 69(9): 4027 - 4035.
[Abstract] [Full Text] [PDF]


Home page
Cancer Prevention ResearchHome page
W. Han, J. J. Gills, R. M. Memmott, S. Lam, and P. A. Dennis
The Chemopreventive Agent Myoinositol Inhibits Akt and Extracellular Signal-Regulated Kinase in Bronchial Lesions from Heavy Smokers
Cancer Prevention Research, April 1, 2009; 2(4): 370 - 376.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
J.-Y. Chung, S.-M. Hong, B. Y. Choi, H. Cho, E. Yu, and S. M. Hewitt
The Expression of Phospho-AKT, Phospho-mTOR, and PTEN in Extrahepatic Cholangiocarcinoma
Clin. Cancer Res., January 15, 2009; 15(2): 660 - 667.
[Abstract] [Full Text] [PDF]


Home page
aacredbookHome page
P. A Dennis
Targeting Akt in Cancer: Promise, Progress, and Potential Pitfalls
Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 25 - 35.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
D. Zhong, X. Liu, K. Schafer-Hales, A. I. Marcus, F. R. Khuri, S.-Y. Sun, and W. Zhou
2-Deoxyglucose induces Akt phosphorylation via a mechanism independent of LKB1/AMP-activated protein kinase signaling activation or glycolysis inhibition
Mol. Cancer Ther., April 1, 2008; 7(4): 809 - 817.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
J. J. Gills, J. LoPiccolo, J. Tsurutani, R. H. Shoemaker, C. J.M. Best, M. S. Abu-Asab, J. Borojerdi, N. A. Warfel, E. R. Gardner, M. Danish, et al.
Nelfinavir, A Lead HIV Protease Inhibitor, Is a Broad-Spectrum, Anticancer Agent that Induces Endoplasmic Reticulum Stress, Autophagy, and Apoptosis In vitro and In vivo
Clin. Cancer Res., September 1, 2007; 13(17): 5183 - 5194.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
C. A. Granville, N. Warfel, J. Tsurutani, M. C. Hollander, M. Robertson, S. D. Fox, T. D. Veenstra, H. J. Issaq, R. I. Linnoila, and P. A. Dennis
Identification of a Highly Effective Rapamycin Schedule that Markedly Reduces the Size, Multiplicity, and Phenotypic Progression of Tobacco Carcinogen-Induced Murine Lung Tumors
Clin. Cancer Res., April 1, 2007; 13(7): 2281 - 2289.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
D. Opel, C. Poremba, T. Simon, K.-M. Debatin, and S. Fulda
Activation of Akt Predicts Poor Outcome in Neuroblastoma
Cancer Res., January 15, 2007; 67(2): 735 - 745.
[Abstract] [Full Text] [PDF]


Home page
Ann OncolHome page
F. Cappuzzo, L. Toschi, G. Tallini, G. L. Ceresoli, I. Domenichini, S. Bartolini, G. Finocchiaro, E. Magrini, G. Metro, A. Cancellieri, et al.
Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib
Ann. Onc., July 1, 2006; 17(7): 1120 - 1127.
[Abstract] [Full Text] [PDF]



About
JCO
 Editorial
Roster
 Advertising
Information
 Librarians &
Institutions
 Rights &
Permissions
 PDA Services

Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online