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  • Oncogenomics
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Identification of H-Ras, RhoA, Rac1 and Cdc42 responsive genes

Oncogene volume 22, pages 2689–2697 (2003)Cite this article

Abstract

The superfamily of small GTP-binding proteins has expanded dramatically in recent years. The Ras family has long been associated with signaling pathways contributing to normal and aberrant cell growth, while Rho-related protein function is to integrate extracellular signals with specific targets regulating cell morphology, cell aggregation, tissue polarity, cell motility and cytokinesis. Recent findings suggest that certain Rho proteins, including RhoA, Rac1 and Cdc42, can also play a role in signal transduction to the nucleus and cell growth control. However, the nature of the genes regulated by Ras and Rho GTPases, as well as their contribution to their numerous biological effects is still largely unknown. To approach these questions, we investigated the global gene expression pattern induced by activated forms of H-Ras, RhoA, Rac1 and Cdc42 using cDNA microarrays comprising 19 117 unique elements. Using this approach, we identified 1184 genes that were up- or downregulated by at least twofold. Hierarchical cluster analysis revealed the existence of patterns of gene regulation both unique and common to H-Ras V12, RhoA QL, Rac1 QL and Cdc42 QL activation. For example, H-Ras V12 upregulated osteopontin and Akt 1, and H-Ras and RhoA stimulated cyclin G1, cyclin-dependent kinase 8, cyclin A2 and HMGI-C, while Rac1 QL and Cdc42 QL upregulated extracellular matrix and cell adhesion proteins such as alpha-actinin 4, procollagen type I and V and neuropilin. Furthermore, H-Ras V12 downregulated by >eightfold 52 genes compared to only three genes by RhoA QL, Rac1 QL and Cdc42 QL. These results provide key information to begin unraveling the complexity of the molecular mechanisms underlying the transforming potential of Ras and Rho proteins, as well as the numerous morphological and cell cycle effects induced by these small GTPases.

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References

  • Bar-Sagi D and Hall A . (2000). Cell, 103, 227–238.

  • Bos JL . (1989). Cancer Res., 49, 4682–4689.

  • Brenner KA, Corbett SA and Schwarzbauer JE . (2000). Oncogene, 19, 3156–3163.

  • Chen H, He Z and Tessier-Lavigne M . (1998). Nat. Neurosci., 1, 436–439.

  • Coso OA, Chiariello M, Yu JC, Teramoto H, Crespo P, Xu N, Miki T and Gutkind JS . (1995). Cell, 81, 1137–1146.

  • Fedele M, Berlingieri MT, Scala S, Chiariotti L, Viglietto G, Rippel V, Bullerdiek J, Santoro M and Fusco A . (1998). Oncogene, 17, 413–418.

  • Fukuhara S, Chikumi H and Gutkind JS . (2001). Oncogene, 20, 1661–1668.

  • Hall A . (1998). Science, 279, 509–514.

  • Hill CS, Wynne J and Treisman R . (1995). Cell, 81, 1159–1170.

  • Liu C, Yao J, Mercola D and Adamson E . (2000). J. Biol. Chem., 275, 20315–20323.

  • Macara IG, Lounsbury KM, Richards SA, McKiernan C and Bar-Sagi D . (1996). FASEB J., 10, 625–630.

  • Malek RL, Irby RB, Guo QM, Lee K, Wong S, He M, Tsai J, Frank B, Quackenbush J, Jove R, Yeatman TJ and Lee NH . (2002). Oncogene, 21, 7256–7265.

  • Michael D and Oren M . (2002). Curr. Opin. Genet. Dev., 12, 53–59.

  • Miyamoto S, Teramoto H, Coso OA, Gutkind JS, Burbelo PD, Akiyama SK and Yamada KM . (1995). J. Cell Biol., 131, 791–805.

  • Narumiya S . (1996). J. Biochem. (Tokyo), 120, 215–228.

  • Nobes CD and Hall A . (1995). Cell, 81, 53–62.

  • Perona R, Esteve P, Jimenez B, Ballestero RP, Ramon Y, Cajal S and Lacal JC . (1993). Oncogene, 8, 1285–1292.

  • Porter AC and Vaillancourt RR . (1998). Oncogene, 17, 1343–1352.

  • Soker S, Takashima S, Miao HQ, Neufeld G and Klagsbrun M . (1998). Cell, 92, 735–745.

  • Takai Y, Sasaki T and Matozaki T . (2001). Physiol. Rev., 81, 153–208.

  • Tanaka TS, Jaradat SA, Lim MK, Kargul GJ, Wang X, Grahovac MJ, Pantano S, Sano Y, Piao Y, Nagaraja R, Doi H, Wood III WH, Becker KG and Ko MS . (2000). Proc. Natl. Acad. Sci. USA, 97, 9127–9132.

  • Teramoto H, Crespo P, Coso OA, Igishi T, Xu N and Gutkind JS . (1996). J. Biol. Chem., 271, 25731–25734.

  • van Leeuwen FN, van der Kammen RA, Habets GG and Collard JG . (1995). Oncogene, 11, 2215–2221.

  • Vara Prasad MV and Dhanasekaran N . (1999). Oncogene, 18, 1639–1642

  • Yang IV, Chen E, Hasseman JP, Liang W, Frank BC, Wang S, Sharov V, Saeed AI, White J, Li J, Lee NH, Yeatman TJ and Quackenbush J . (2002). Genome Biol., 3, research 0062.

  • Zhang J, Takahashi K, Takahashi F, Shimizu K, Ohshita F, Kameda Y, Maeda K, Nishio K and Fukuchi Y . (2001). Cancer Lett., 171, 215–222.

  • Zentner MD, Lin HH, Deng HT, Kim KJ, Shih HM and Ann DK . (2001). J. Biol. Chem., 276, 29805–29815.

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Authors and Affiliations

  1. Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, 20892-4330, MD, USA

    Hidemi Teramoto, Maria Domenica Castellone & J Silvio Gutkind

  2. Department of Functional Genomics, The Institute for Genomic Research, Rockville, 20850, MD, USA

    Renae L Malek, Babak Behbahani & Norman H Lee

  3. Department of Pharmacology, The George Washington University Medical Center, DC 20037, Washington, USA

    Norman H Lee

Authors
  1. Hidemi Teramoto
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  2. Renae L Malek
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  4. Maria Domenica Castellone
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  5. Norman H Lee
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  6. J Silvio Gutkind
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Correspondence to J Silvio Gutkind.

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Teramoto, H., Malek, R., Behbahani, B. et al. Identification of H-Ras, RhoA, Rac1 and Cdc42 responsive genes. Oncogene 22, 2689–2697 (2003). https://doi.org/10.1038/sj.onc.1206364

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