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 Lee, W.-P.
Right arrow Articles by Hung, M.-C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, W.-P.
Right arrow Articles by Hung, M.-C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 1999, p. 8075-8082, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Axl-Gas6 Interaction Counteracts E1A-Mediated Cell Growth Suppression and Proapoptotic Activity

Wei-Ping Lee,1 Yong Liao,1 Dan Robinson,2 Hsing-Jien Kung,2 Edison T. Liu,3 and Mien-Chie Hung1,*

Department of Cancer Biology, Section of Molecular Cell Biology and Breast Cancer Research Program, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 770301; The University of California-Davis Cancer Center, Sacramento, California 958172; and Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 208923

Received 20 July 1999/Returned for modification 31 August 1999/Accepted 16 September 1999

The adenovirus type 5 early region 1A gene (E1A) has previously been known as an immortalization oncogene because E1A is required for transforming oncogenes, such as ras and E1B, to transform cells in primary cultures. However, E1A has also been shown to downregulate the overexpression of the Her-2/neu oncogene, resulting in suppression of transformation and tumorigenesis induced by that oncogene. In addition, E1A is able to promote apoptosis induced by anticancer drugs, irradiation, and serum deprivation. Many tyrosine kinases, such as the epidermal growth factor receptor, Her-2/Neu, Src, and Axl, are known to play a role in oncogenic signals in transformed cells. To study the mechanism underlying the E1A-mediated tumor-suppressing function, we exploited a modified tyrosine kinase profile assay (D. Robinson, F. Lee, T. Pretlow, and H.-J. Kung, Proc. Natl. Acad. Sci. USA 93:5958-5962, 1996) to identify potential tyrosine kinases regulated by E1A. Reverse transcription (RT)-PCR products were synthesized with two degenerate primers derived from the conserved motifs of various tyrosine kinases. A tyrosine kinase downregulated by E1A was identified by analyzing the AluI-digested RT-PCR products. We isolated the DNA fragment of interest and found that E1A negatively regulated the expression of the transforming receptor tyrosine kinase Axl at the transcriptional level. To study whether downregulation of the Axl receptor is involved in E1A-mediated growth suppression, we transfected axl cDNA into E1A-expressing cells (ip1-E1A) to establish cells that overexpressed Axl. The Axl ligand Gas6 triggered a greater mitogenic effect in these ip1-E1A-Axl cells than in ip1-E1A control cells and protected the Axl-expressing cells from serum deprivation-induced apoptosis. These results indicate that downregulation of the Axl receptor by E1A is involved in E1A-mediated growth suppression and E1A-induced apoptosis and thereby contributes to E1A's antitumor activities.

* Corresponding author. Mailing address: 1515 Holcombe Blvd., Section of Molecular Cell Biology Box 108, Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030. Phone: (713) 792-3668. Fax: (713) 794-0209. E-mail: mchung{at}notes.mdacc.tmc.edu.

Molecular and Cellular Biology, December 1999, p. 8075-8082, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Revil, T., Toutant, J., Shkreta, L., Garneau, D., Cloutier, P., Chabot, B. (2007). Protein Kinase C-Dependent Control of Bcl-x Alternative Splicing. Mol. Cell. Biol. 27: 8431-8441 [Abstract] [Full Text]  
  • Korshunov, V. A., Daul, M., Massett, M. P., Berk, B. C. (2007). Axl Mediates Vascular Remodeling Induced by Deoxycorticosterone Acetate Salt Hypertension. Hypertension 50: 1057-1062 [Abstract] [Full Text]  
  • Korshunov, V. A., Mohan, A. M., Georger, M. A., Berk, B. C. (2006). Axl, A Receptor Tyrosine Kinase, Mediates Flow-Induced Vascular Remodeling. Circ. Res. 98: 1446-1452 [Abstract] [Full Text]  
  • Bartholomeusz, C., Itamochi, H., Yuan, L. X.H., Esteva, F. J., Wood, C. G., Terakawa, N., Hung, M.-C., Ueno, N. T. (2005). Bcl-2 Antisense Oligonucleotide Overcomes Resistance to E1A Gene Therapy in a Low HER2-Expressing Ovarian Cancer Xenograft Model. Cancer Res. 65: 8406-8413 [Abstract] [Full Text]  
  • Rau, K-M, Kang, H-Y, Cha, T-L, Miller, S A, Hung, M-C (2005). The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers. Endocr Relat Cancer 12: 511-532 [Abstract] [Full Text]  
  • Shao, R., Lee, D.-F., Wen, Y., Ding, Y., Xia, W., Ping, B., Yagita, H., Spohn, B., Hung, M.-C. (2005). E1A Sensitizes Cancer Cells to TRAIL-Induced Apoptosis through Enhancement of Caspase Activation. Mol Cancer Res 3: 219-226 [Abstract] [Full Text]  
  • Wu, Y.-M., Robinson, D. R., Kung, H.-J. (2004). Signal Pathways in Up-regulation of Chemokines by Tyrosine Kinase MER/NYK in Prostate Cancer Cells. Cancer Res. 64: 7311-7320 [Abstract] [Full Text]  
  • Liao, Y., Hung, M.-C. (2003). Regulation of the Activity of p38 Mitogen-Activated Protein Kinase by Akt in Cancer and Adenoviral Protein E1A-Mediated Sensitization to Apoptosis. Mol. Cell. Biol. 23: 6836-6848 [Abstract] [Full Text]  
  • Sun, W. S., Fujimoto, J., Tamaya, T. (2003). Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases Axl and Sky in human uterine endometrial cancers. Ann Oncol 14: 898-906 [Abstract] [Full Text]  
  • Xia, L., Robinson, D., Ma, A.-H., Chen, H.-C., Wu, F., Qiu, Y., Kung, H.-J. (2002). Identification of Human Male Germ Cell-associated Kinase, a Kinase Transcriptionally Activated by Androgen in Prostate Cancer Cells. J. Biol. Chem. 277: 35422-35433 [Abstract] [Full Text]  
  • Meric, F., Lee, W.-P., Sahin, A., Zhang, H., Kung, H.-J., Hung, M.-C. (2002). Expression Profile of Tyrosine Kinases in Breast Cancer. Clin. Cancer Res. 8: 361-367 [Abstract] [Full Text]  
  • Zantek, N. D., Walker-Daniels, J., Stewart, J., Hansen, R. K., Robinson, D., Miao, H., Wang, B., Kung, H.-J., Bissell, M. J., Kinch, M. S. (2001). MCF-10A-NeoST: A New Cell System for Studying Cell-ECM and Cell-Cell Interactions in Breast Cancer. Clin. Cancer Res. 7: 3640-3648 [Abstract] [Full Text]  
  • Goruppi, S., Chiaruttini, C., Ruaro, M. E., Varnum, B., Schneider, C. (2001). Gas6 Induces Growth, {beta}-Catenin Stabilization, and T-Cell Factor Transcriptional Activation in Contact-Inhibited C57 Mammary Cells. Mol. Cell. Biol. 21: 902-915 [Abstract] [Full Text]  
  • Shao, R., Xia, W., Hung, M.-C. (2000). Inhibition of Angiogenesis and Induction of Apoptosis Are Involved in E1A-mediated Bystander Effect and Tumor Suppression. Cancer Res. 60: 3123-3126 [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»