Abstract
We have previously shown that expression of active Rac1 and Cdc4Hs inhibits skeletal muscle cell differentiation. We show here, by bromodeoxyuridine incorporation and cyclin D1 expression, that the expression of active Rac1 and Cdc42Hs but not RhoA impairs cell cycle exit of L6 myoblasts cultured in differentiation medium. Furthermore, expression of activated forms of Rac1 and Cdc42Hs elicits the loss of cell contact inhibition and anchorage-dependent growth as measured by focus forming activity and growth in soft agar. RhoA was once again not found to have this effect. We found a constitutive Rac1 and Cdc42Hs activation in three human rhabdomyosarcoma-derived cell lines, one of the most common causes of solid tumours arising from muscle precursors during childhood. Finally, dominant negative forms of Rac1 and Cdc42Hs inhibit cell proliferation of the RD rhabdomyosarcoma cell line. These data suggest an important role for the small GTPases Rac1 and Cdc42Hs in the generation of skeletal muscle tumours.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Carnac G, Primig M, Kitzmann M, Chafey P, Tuil D, Lamb N, Fernandez A . 1998 Mol. Biol. Cell. 9: 1891–1902
Chardin P, Yeramian P, Madaule P, Tavitian A . 1985 Int. J. Cancer 35: 647–652
Clark GJ, Westwick JK, Der CJ . 1997 J. Biol. Chem. 272: 1677–1681
Cuenda A, Cohen P . 1999 J. Biol. Chem. 274: 4341–4346
Fritz G, Just I, Kaina B . 1999 Int. J. Cancer 81: 682–687
Gallo R, Serafini M, Castellani L, Falcone G, Alema S . 1999 Mol. Biol. Cell. 10: 3137–3150
Gauthier RC, Vignal E, Meriane M, Roux P, Montcourier P, Fort P . 1998 Mol. Biol. Cell. 9: 1379–1394
Gauthier-Rouviere C, Cavadore JC, Blanchard JM, Lamb NJ, Fernandez A . 1991 Cell Regul. 2: 575–588
Heller H, Gredinger E, Bengal E . 2001 J. Biol. Chem. 6: 6–
Izawa I, Amano M, Chihara K, Yamamoto T, Kaibuchi K . 1998 Oncogene 17: 2863–2871
Joneson T, Bar-Sagi D . 1998 J. Biol. Chem. 273: 17991–17994
Khosravi-Far R, Solski PA, Clark GJ, Kinch MS, Der CJ . 1995 Mol. Cell. Biol. 15: 6443–6453
Kinch MS, Clark GJ, Der CJ, Burridge K . 1995 J. Cell. Biol. 130: 461–471
Kozma R, Ahmed S, Best A, Lim L . 1995 Mol. Cell. Biol. 15: 1942–1952
Lassar AB, Skapek SX, Novitch B . 1994 Curr. Opin. Cell. Biol. 6: 788–794
Mangues R, Pellicer A . 1992 Semin. Cancer Biol. 3: 229–239
Meriane M, Roux P, Primig M, Fort P, Gauthier-Rouviere C . 2000 Mol. Biol. Cell. 11: 2513–2528
Mira JP, Benard V, Groffen J, Sanders LC, Knaus UG . 2000 Proc. Natl. Acad. Sci. USA 97: 185–189
Olson MF, Ashworth A, Hall A . 1995 Science 269: 1270–1272
Puri PL, Wu Z, Zhang P, Wood LD, Bhakta KS, Han J, Feramisco JR, Karin M, Wang JY . 2000 Genes Dev. 14: 574–584
Qiu RG, Abo A, McCormick F, Symons M . 1997 Mol. Cell. Biol. 17: 3449–3458
Qiu RG, Chen J, McCormick F, Symons M . 1995 Proc. Natl. Acad. Sci. USA 92: 11781–11785
Rao SS, Kohtz DS . 1995 J. Biol. Chem. 270: 4093–4100
Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A . 1992 Cell 70: 401–410
Roux P, Gauthier-Rouviere C, Doucet-Brutin S, Fort P . 1997 Curr. Biol. 7: 629–637
Sahai E, Olson MF, Marshall CJ . 2001 EMBO J. 20: 755–766
Takano H, Komuro I, Oka T, Shiojima I, Hiroi Y, Mizuno T, Yazaki Y . 1998 Mol. Cell. Biol. 18: 1580–1589
Van Aelst L, D'Souza-Schorey C . 1997 Genes Dev. 11: 2295–2322
Vandromme M, Gauthier RC, Carnac G, Lamb N, Fernandez A . 1992 J. Cell. Biol. 118: 1489–1500
Walsh K, Perlman H . 1997 Curr. Opin. Genet. Dev. 7: 597–602
Wei L, Zhou W, Croissant JD, Johansen FE, Prywes R, Balasubramanyam A, Schwartz RJ . 1998 J. Biol. Chem. 273: 30287–30294
Westwick JK, Lambert QT, Clark GJ, Symons M, Van Aelst L, Pestell RG, Der CJ . 1997 Mol. Cell. Biol. 17: 1324–1335
Wu Z, Woodring PJ, Bhakta KS, Tamura K, Wen F, Feramisco JR, Karin M, Wang JY, Puri PL . 2000 Mol. Cell. Biol. 20: 3951–3964
Zetser A, Gredinger E, Bengal E . 1999 J. Biol. Chem. 274: 5193–5200
Zhong C, Kinch MS, Burridge K . 1997 Mol. Biol. Cell. 8: 2329–2344
Zohn IM, Campbell SL, Khosravi-Far R, Rossman KL, Der CJ . 1998 Oncogene 17: 1415–1438
Acknowledgements
We thank Anne Blangy and Emmanuel Vignal for constant support. We also thank J Collard and M Schwartz for GST-Pak and GST-Rhotekin, respectively and A Eychene for GST-RafGDSRBD. We would like to thank Atta Behfar for critically reading the manuscript. This work was supported by institutional grants from the Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Medicale, and contracts from the Association Francaise pour la Recherche contre le Cancer (ARC contrat n°5568), the Ligue Nationale Contre le Cancer (‘équipe labellisée’) and the Association Francaise contre les myopathies.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Meriane, M., Charrasse, S., Comunale, F. et al. Participation of small GTPases Rac1 and Cdc42Hs in myoblast transformation. Oncogene 21, 2901–2907 (2002). https://doi.org/10.1038/sj.onc.1205396
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205396
Keywords
This article is cited by
-
RhoE controls myoblast alignment prior fusion through RhoA and ROCK
Cell Death & Differentiation (2008)
-
Variation in cadherins and catenins expression is linked to both proliferation and transformation of Rhabdomyosarcoma
Oncogene (2004)
-
The PAX8/PPARγ fusion oncoprotein transforms immortalized human thyrocytes through a mechanism probably involving wild-type PPARγ inhibition
Oncogene (2004)