| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cell, Tumor, and Stem Cell Biology |
B Pathway by Astrocyte Elevated Gene-1: Implications for Tumor Progression and Metastasis
Departments of 1 Pathology, 2 Urology, and 3 Neurosurgery, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York and 4 Department of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia
Requests for reprints: Paul B. Fisher, Department of Pathology, College of Physicians and Surgeons, Columbia University Medical Center, 630 West 168th Street, BB-1501, New York, NY 10032. Phone: 212-305-3642; -3966; Fax: 212-305-8177; E-mail: pbf1{at}columbia.edu.
Astrocyte elevated gene-1 (AEG-1) was initially identified as an HIV-1- and tumor necrosis factor
(TNF-
)inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. Interestingly, AEG-1 expression is elevated in subsets of breast cancer, glioblastoma multiforme and melanoma cells and AEG-1 cooperates with Ha-ras to promote transformation of immortalized melanocytes. Activation of the transcription factor nuclear factor
B (NF-
B), a TNF-
downstream signaling component, is associated with several human illnesses, including cancer, and NF-
B controls the expression of multiple genes involved in tumor progression and metastasis. We now document that AEG-1 is a significant positive regulator of NF-
B. Enhanced expression of AEG-1 via a replication-incompetent adenovirus (Ad.AEG-1) in HeLa cells markedly increased binding of the transcriptional activator p50/p65 complex of NF-
B. The NF-
B activation induced by AEG-1 corresponded with degradation of I
B
and nuclear translocation of p65 that resulted in the induction of NF-
B downstream genes. Infection with an adenovirus expressing the mt32I
B
superrepressor (Ad.I
B
-mt32), which prevents p65 nuclear translocation, inhibited AEG-1-induced enhanced agar cloning efficiency and increased matrigel invasion of HeLa cells. We also document that TNF-
treatment resulted in nuclear translocation of both AEG-1 and p65 wherein these two proteins physically interacted, suggesting a potential mechanism by which AEG-1 could activate NF-
B. Our findings suggest that activation of NF-
B by AEG-1 could represent a key molecular mechanism by which AEG-1 promotes anchorage-independent growth and invasion, two central features of the neoplastic phenotype. (Cancer Res 2006; 66(3): 1509-16)
This article has been cited by other articles:
![]() |
S.-G. Lee, Z.-Z. Su, L. Emdad, P. Gupta, D. Sarkar, A. Borjabad, D. J. Volsky, and P. B. Fisher Mechanism of Ceftriaxone Induction of Excitatory Amino Acid Transporter-2 Expression and Glutamate Uptake in Primary Human Astrocytes J. Biol. Chem., May 9, 2008; 283(19): 13116 - 13123. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Sarkar, E. S. Park, L. Emdad, S.-G. Lee, Z.-z. Su, and P. B. Fisher Molecular Basis of Nuclear Factor-{kappa}B Activation by Astrocyte Elevated Gene-1 Cancer Res., March 1, 2008; 68(5): 1478 - 1484. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. Britt, S. Ash, and D. Yang Defining a role for LYRIC in NF-kappaB signaling and prostate tumor progression FASEB J, April 1, 2007; 21(6): A1151 - A1151. |
||||
![]() |
H. Boukerche, Z.-z. Su, L. Emdad, D. Sarkar, and P. B. Fisher mda-9/Syntenin Regulates the Metastatic Phenotype in Human Melanoma Cells by Activating Nuclear Factor-{kappa}B Cancer Res., February 15, 2007; 67(4): 1812 - 1822. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Loewe, T. Valero, S. Kremling, B. Pratscher, R. Kunstfeld, H. Pehamberger, and P. Petzelbauer Dimethylfumarate Impairs Melanoma Growth and Metastasis Cancer Res., December 15, 2006; 66(24): 11888 - 11896. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-G. Lee, Z.-Z. Su, L. Emdad, D. Sarkar, and P. B. Fisher Astrocyte elevated gene-1 (AEG-1) is a target gene of oncogenic Ha-ras requiring phosphatidylinositol 3-kinase and c-Myc PNAS, November 14, 2006; 103(46): 17390 - 17395. [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 |