Molecular Cancer Therapeutics CTRC-AACR San Antonio Breast Cancer Symposium
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 Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yang, H.
Right arrow Articles by Vassilev, L. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, H.
Right arrow Articles by Vassilev, L. T.
Mol Cancer Ther. 2003;2:1023-1029
© 2003 American Association for Cancer Research

Macrophage inhibitory cytokine-1: A novel biomarker for p53 pathway activation

Hong Yang1, Zoran Filipovic1, David Brown2, Samuel N. Breit2 and Lyubomir T. Vassilev1

1 Discovery Oncology, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ, 2 Centre for Immunology, St. Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia

Requests for reprints:Lyubomir T. Vassilev, Discovery Oncology, Roche Research Center, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110. Phone: (973) 235-8106; Fax: (973) 235-6185. E-mail: lyubomir.vassilev{at}roche.com

The p53 tumor suppressor protein plays a key function in the cellular response to stress by activating a subset of genes responsible for cell cycle arrest and apoptosis. Activation of the p53 pathway in tumor cells has been proposed as a novel approach to cancer therapy and substantial efforts have been dedicated to the discovery of pharmacological p53 activators. Here, we show that the transforming growth factor-ß superfamily cytokine, macrophage inhibitory cytokine-1 (MIC-1), can serve as a secreted biomarker for activation of p53 in both cellular and xenograft models of human cancer. Using doxorubicin treatment in the HCT116 colon cancer cell line, we have shown that MIC-1 secretion into culture media is correlated with p53 pathway activation as measured by the up-regulation of its downstream transcriptional target p21. When transplanted into nude mice, HCT116 cells continued to secret human MIC-1 and mouse plasma levels correlated well with tumor volume. Treatment of these animals with a single dose of doxorubicin led to activation of the p53 pathway and a nearly 4-fold elevation of the plasma MIC-1 level, which was paralleled by p21 induction in the tumor xenografts. Estimation of MIC-1 concentration, both in vivo and in vitro, represents a novel tool for the study of p53 pathway and development of p53-activating therapeutics.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Grant Support:National Health and Medical Research Council of Australia; St. Vincent's Hospital, Sydney; Meriton Apartments Pty Ltd. through an R&D syndicate arranged by Macquarie Bank Limited; and New South Wales Health Research and Development Infrastructure.

Received 3/13/03; revised 7/25/03; accepted 7/31/03.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
S. Shangary and S. Wang
Targeting the MDM2-p53 Interaction for Cancer Therapy
Clin. Cancer Res., September 1, 2008; 14(17): 5318 - 5324.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S.-L. Chiang, S.-S. Jiang, Y.-J. Wang, H.-C. Chiang, P.-H. Chen, H.-P. Tu, K.-Y. Ho, Y.-S. Tsai, I-S. Chang, and Y.-C. Ko
Characterization of Arecoline-Induced Effects on Cytotoxicity in Normal Human Gingival Fibroblasts by Global Gene Expression Profiling
Toxicol. Sci., November 1, 2007; 100(1): 66 - 74.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. T.-C. Chang, S.-H. Chan, C.-Y. Lin, T.-Y. Lin, H.-M. Wang, C.-T. Liao, T.-H. Wang, L.-Y. Lee, and A.-J. Cheng
Differentially expressed genes in radioresistant nasopharyngeal cancer cells: gp96 and GDF15
Mol. Cancer Ther., August 1, 2007; 6(8): 2271 - 2279.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
P. Secchiero, F. Corallini, A. Gonelli, R. Dell'Eva, M. Vitale, S. Capitani, A. Albini, and G. Zauli
Antiangiogenic Activity of the MDM2 Antagonist Nutlin-3
Circ. Res., January 5, 2007; 100(1): 61 - 69.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. R. Bauskin, D. A. Brown, T. Kuffner, H. Johnen, X. W. Luo, M. Hunter, and S. N. Breit
Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer.
Cancer Res., May 15, 2006; 66(10): 4983 - 4986.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
K. K. Rasiah, J. G. Kench, M. Gardiner-Garden, A. V. Biankin, D. Golovsky, P. C. Brenner, R. Kooner, G. F. O'Neill, J. J. Turner, W. Delprado, et al.
Aberrant neuropeptide y and macrophage inhibitory cytokine-1 expression are early events in prostate cancer development and are associated with poor prognosis.
Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 711 - 716.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Tovar, J. Rosinski, Z. Filipovic, B. Higgins, K. Kolinsky, H. Hilton, X. Zhao, B. T. Vu, W. Qing, K. Packman, et al.
From the Cover: Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: Implications for therapy
PNAS, February 7, 2006; 103(6): 1888 - 1893.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. A. Brown, C. Stephan, R. L. Ward, M. Law, M. Hunter, A. R. Bauskin, J. Amin, K. Jung, E. P. Diamandis, G. M. Hampton, et al.
Measurement of Serum Levels of Macrophage Inhibitory Cytokine 1 Combined with Prostate-Specific Antigen Improves Prostate Cancer Diagnosis
Clin. Cancer Res., January 1, 2006; 12(1): 89 - 96.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
B. L. Hood, M. M. Darfler, T. G. Guiel, B. Furusato, D. A. Lucas, B. R. Ringeisen, I. A. Sesterhenn, T. P. Conrads, T. D. Veenstra, and D. B. Krizman
Proteomic Analysis of Formalin-fixed Prostate Cancer Tissue
Mol. Cell. Proteomics, November 1, 2005; 4(11): 1741 - 1753.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
T. Kosakowska-Cholody, W. M. Cholody, A. Monks, B. A. Woynarowska, and C. J. Michejda
WMC-79, a potent agent against colon cancers, induces apoptosis through a p53-dependent pathway
Mol. Cancer Ther., October 1, 2005; 4(10): 1617 - 1627.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
S. Malatos, H. Neubert, A. T. Kicman, and R. K. Iles
Identification of Placental Transforming Growth Factor-{beta} and Bikunin Metabolites as Contaminants of Pharmaceutical Human Chorionic Gonadotrophin Preparations by Proteomic Techniques
Mol. Cell. Proteomics, July 1, 2005; 4(7): 984 - 992.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
W. Wollmann, M. L. Goodman, P. Bhat-Nakshatri, H. Kishimoto, R. J. Goulet Jr, S. Mehrotra, A. Morimiya, S. Badve, and H. Nakshatri
The macrophage inhibitory cytokine integrates AKT/PKB and MAP kinase signaling pathways in breast cancer cells
Carcinogenesis, May 1, 2005; 26(5): 900 - 907.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. R. Bauskin, D. A. Brown, S. Junankar, K. K. Rasiah, S. Eggleton, M. Hunter, T. Liu, D. Smith, T. Kuffner, G. J. Pankhurst, et al.
The Propeptide Mediates Formation of Stromal Stores of PROMIC-1: Role in Determining Prostate Cancer Outcome
Cancer Res., March 15, 2005; 65(6): 2330 - 2336.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Thompson, C. Tovar, H. Yang, D. Carvajal, B. T. Vu, Q. Xu, G. M. Wahl, D. C. Heimbrook, and L. T. Vassilev
Phosphorylation of p53 on Key Serines Is Dispensable for Transcriptional Activation and Apoptosis
J. Biol. Chem., December 17, 2004; 279(51): 53015 - 53022.
[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 Meeting Abstracts Online
Copyright © 2003 by the American Association for Cancer Research.