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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lasorella, A.
Right arrow Articles by Iavarone, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lasorella, A.
Right arrow Articles by Iavarone, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2005, p. 3563-3574, Vol. 25, No. 9
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.9.3563-3574.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Id2 Mediates Tumor Initiation, Proliferation, and Angiogenesis in Rb Mutant Mice

Anna Lasorella,1,2,3 Gerson Rothschild,3 Yoshifumi Yokota,4 Robert G. Russell,5 and Antonio Iavarone2,3,6*

Department of Pediatrics,1 Department of Pathology,2 Institute for Cancer Genetics,3 Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, New York,6 Department of Biochemistry, Fukui Medical University, Fukui Japan,4 Lombardi Cancer Center, Department of Oncology, Georgetown University, Washington, DC5

Received 30 August 2004/ Returned for modification 9 November 2004/ Accepted 18 January 2005

The inhibitor of differentiation Id2 is a target of the retinoblastoma (Rb) protein during mouse embryogenesis. In Rb+/– mice, LOH at the wild-type Rb allele initiates pituitary adenocarcinoma, a tumor derived from embryonic melanotropes. Here we identify a critical role for Id2 in initiation, growth, and angiogenesis of pituitary tumors from Rb+/– mice. We show that proliferation and differentiation are intimately coupled in Rb+/– pituitary cells before tumor initiation. In Id2-null pituitaries, premature activation of basic helix-loop-helix-mediated transcription and expression of the cdk inhibitor p27Kip1 impairs the proliferation of melanotropes and tumor initiation. Without Id2, Rb+/– mice have fewer early tumor lesions and a markedly decreased proliferation rate of the tumor foci. Expression of Id2 by pituitary tumor cells promotes growth and angiogenesis by functioning as a master regulator of vascular endothelial growth factor (VEGF). In human neuroblastoma, the N-Myc-driven expression of Id2 is sufficient and necessary for expression of VEGF. These results establish that aberrant Id2 activity directs initiation and progression of embryonal cancer.

* Corresponding author. Mailing address: Institute for Cancer Genetics, Columbia University, 1150 St. Nicholas Ave., New York, NY 10032. Phone: (212) 851-5245. Fax: (212) 851-5267. E-mail: ai2102{at}columbia.edu.

Molecular and Cellular Biology, May 2005, p. 3563-3574, Vol. 25, No. 9
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.9.3563-3574.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Trabosh, V. A., Divito, K. A., D. Aguda, B., Simbulan-Rosenthal, C. M., Rosenthal, D. S. (2009). Sequestration of E12/E47 and suppression of p27KIP1 play a role in Id2-induced proliferation and tumorigenesis. Carcinogenesis 30: 1252-1259 [Abstract] [Full Text]  
  • Han, W., Wu, Z., Zhao, Y., Meng, Y., Si, Y., Yang, J., Fu, X., Yu, L. (2009). FHL2 interacts with and acts as a functional repressor of Id2 in human neuroblastoma cells. Nucleic Acids Res 0: gkp332v1-gkp332 [Abstract] [Full Text]  
  • Yan, W., Liu, G., Scoumanne, A., Chen, X. (2008). Suppression of Inhibitor of Differentiation 2, a Target of Mutant p53, Is Required for Gain-of-Function Mutations. Cancer Res. 68: 6789-6796 [Abstract] [Full Text]  
  • Tsunedomi, R., Iizuka, N., Tamesa, T., Sakamoto, K., Hamaguchi, T., Somura, H., Yamada, M., Oka, M. (2008). Decreased ID2 Promotes Metastatic Potentials of Hepatocellular Carcinoma by Altering Secretion of Vascular Endothelial Growth Factor. Clin. Cancer Res. 14: 1025-1031 [Abstract] [Full Text]  
  • Ye, F.-C., Blackbourn, D. J., Mengel, M., Xie, J.-P., Qian, L.-W., Greene, W., Yeh, I-T., Graham, D., Gao, S.-J. (2007). Kaposi's Sarcoma-Associated Herpesvirus Promotes Angiogenesis by Inducing Angiopoietin-2 Expression via AP-1 and Ets1. J. Virol. 81: 3980-3991 [Abstract] [Full Text]  
  • Hamik, A., Wang, B., Jain, M. K. (2006). Transcriptional Regulators of Angiogenesis. Arterioscler. Thromb. Vasc. Bio. 26: 1936-1947 [Abstract] [Full Text]  
  • Rothschild, G., Zhao, X., Iavarone, A., Lasorella, A. (2006). E Proteins and Id2 Converge on p57Kip2 To Regulate Cell Cycle in Neural Cells.. Mol. Cell. Biol. 26: 4351-4361 [Abstract] [Full Text]  
  • Lasorella, A., Iavarone, A. (2006). The protein ENH is a cytoplasmic sequestration factor for Id2 in normal and tumor cells from the nervous system. Proc. Natl. Acad. Sci. USA 103: 4976-4981 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»