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The Ras-related protein AGS1/RASD1 suppresses cell growth

Oncogene volume 23, pages 5858–5863 (2004)Cite this article

Abstract

AGS1/RASD1 is a Ras-related protein identified as a dexamethasone-inducible cDNA and as a signal regulator in various functional and protein-interaction screens. As an initial approach to define the role of AGS1/RASD1 as a Ras-family member, we determined its influence on cell growth/survival. In clonogenic assays with NIH-3T3 murine fibroblast cells, the MCF-7 human breast cancer cell line and the human lung adenocarcinoma cell line A549, AGS1/RASD1 markedly diminished the number of G418-resistant colonies, whereas the Ras subgroup member K-Ras was without effect. A549 cell infection with adenovirus engineered to express AGS1/RASD1 (Ad.AGS1) inhibited log phase growth in vitro and increased the percentage of cells undergoing apoptosis. The anti-growth action was also observed in vivo as the expression of AGS1/RASD1 inhibited the subcutaneous tumor growth of A549 cells in athymic nude mice. These data indicate that AGS1/RASD1, a member of the Ras superfamily of small G-proteins that often promotes cell growth and tumor expansion, plays an active role in preventing aberrant cell growth.

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Acknowledgements

This work was supported by awards (MH90531 (SML) and NS24821 (SML)) from the National Institutes of Health. SML is greatly appreciative of the support provided by a Research Scholar Award from Yamanouchi Pharmaceutical Company, Inc. and the David R Bethune/Lederle Laboratories Professorship in Pharmacology. SML and GV appreciate the technical assistance provided by Maureen Fallon and Dallis Green, as well as the efforts of the LSUHSC cell culture core manager Joelle Finley, the LSUHSC vector core manager Robert Kutner and Nick Lanson (Gene Therapy/Medicine, LSUHSC). We also thank Aaron Adamson (Department of Biochemistry, LSUHSC) and Constance Porretta (Gene Therapy/Medicine, LSUHSC) for assistance in FACS analysis. Dr Catalina Ribas was involved in the isolation of rat AGS1/RASD1 from a rat brain cDNA library. We also appreciate the comments, support and reagents provided by Drs Emir Duzic (Millennium Pharmaceuticals Inc, Cambridge, MA), SM Hill (Tulane Cancer Center, New Orleans, LA), Andrew D Catling, Hamid Boulares, Joe B Blumer and Frank Park (Department of Pharmacology, LSUHSC).

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Authors and Affiliations

  1. Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, 70112, LA, USA

    Govindan Vaidyanathan & Stephen M Lanier

  2. Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, 44272, OH, USA

    Mary J Cismowski

  3. Department of Medicine and Genetics, Louisiana State University Health Sciences Center, USA

    Guoshun Wang

  4. Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, 26506, WV, USA

    Timothy S Vincent

  5. Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, USA

    Kevin D Brown

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  1. Govindan Vaidyanathan
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  2. Mary J Cismowski
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  3. Guoshun Wang
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  4. Timothy S Vincent
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  5. Kevin D Brown
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  6. Stephen M Lanier
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Correspondence to Stephen M Lanier.

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Vaidyanathan, G., Cismowski, M., Wang, G. et al. The Ras-related protein AGS1/RASD1 suppresses cell growth. Oncogene 23, 5858–5863 (2004). https://doi.org/10.1038/sj.onc.1207774

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