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Tumor suppressor function of Betaig-h3 gene in radiation carcinogenesis.

Abstract
Interaction between cell and extracellular matrix (ECM) plays a crucial role in tumor invasiveness and metastasis. Using an immortalized human bronchial epithelial (BEP2D) cell model, we showed previously that expression of a list of genes including Betaig-h3 (induced by transforming growth factor-beta), DCC (deleted in colorectal cancer), p21(cipl), c-fos, Heat shock protein (HSP27) and cytokeratin 14 were differentially expressed in several independently generated, radiation-induced tumor cell lines (TL1-TL5) relative to parental BEP2D cells. Our previous data further demonstrated that loss of tumor suppressor gene(s) as a likely mechanism of radiation carcinogenesis. In the present study, we chose Betaig-h3 and DCC that were downregulated in tumorigenic cells for further study. Restored expression of Betaig-h3 gene, not DCC gene, by transfecting cDNA into tumor cells resulted in a significant reduction in tumor growth. While integrin receptor alpha 5 beta 1 was overexpressed in tumor cells, its expression was corrected to the level found in control BEP2D cells after Betaig-h3 transfection. These data suggest that Betaig-h3 gene is involved in tumor progression by regulating integrin alpha 5 beta 1 receptor. Furthermore, exogenous TGF- beta 1 induced expression of Betaig-h3 gene and inhibited the growth of both control and tumorigenic BEP2D cells. Therefore, downregulation of Betaig-h3 gene may results from the decreased expression of upstream mediators such as TGF-beta. The findings provide strong evidence that the Betaig-h3 gene has tumor suppressor function in radiation-induced tumorigenic human bronchial epithelial cells and suggest a potential target for interventional therapy.
AuthorsY L Zhao, C Q Piao, T K Hei
JournalAdvances in space research : the official journal of the Committee on Space Research (COSPAR) (Adv Space Res) Vol. 31 Issue 6 Pg. 1575-82 ( 2003) ISSN: 0273-1177 [Print] England
PMID12971413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Copyrightc2003 COSPAR. Published by Elsevier Science Ltd. All rights reserved.
Chemical References
  • Extracellular Matrix Proteins
  • Integrin alpha5beta1
  • Transforming Growth Factor beta
  • betaIG-H3 protein
Topics
  • Alpha Particles
  • Animals
  • Bronchi (cytology)
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic (genetics, metabolism, pathology)
  • Epithelial Cells (radiation effects)
  • Extracellular Matrix (genetics, metabolism, physiology)
  • Extracellular Matrix Proteins (biosynthesis, genetics, physiology)
  • Gene Expression (radiation effects)
  • Genes, DCC
  • Genes, Tumor Suppressor
  • Humans
  • Integrin alpha5beta1 (genetics, metabolism, physiology)
  • Mice
  • Mice, Nude
  • Neoplasms, Radiation-Induced (genetics, metabolism, pathology)
  • Transforming Growth Factor beta
  • Tumor Cells, Cultured

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