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.
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Authors | Y L Zhao, C Q Piao, T K Hei |
Journal | Advances 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 |
PMID | 12971413
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Copyright | c2003 COSPAR. Published by Elsevier Science Ltd. All rights reserved. |
Chemical References |
- Extracellular Matrix Proteins
- Integrin alpha5beta1
- Transforming Growth Factor beta
- betaIG-H3 protein
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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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