Carcinogenesis Advance Access published online on November 21, 2003
Carcinogenesis, doi:10.1093/carcin/bgh026
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CANCER BIOLOGY
1 Department of Pathology and NYU Cancer Institute, New York University School of Medicine, New York, NY, 10016
* Corresponding author. E-mail: pellia01{at}med.nyu.edu.
Received 21 August 2003
; revised 10 November 2003
; accepted 11 November 2003
Ras proteins have been found mutated in about one third of human tumors. In vitro, Ras has been shown to regulate distinct and contradictory effects, such as cellular proliferation and apoptosis. Nonetheless, the effects that the wild-type protein elicits in tumorigenesis are poorly understood. Depending on the type of tissue, Ras proto-oncogenes appear to either promote or inhibit the tumor phenotype. In this report, we treated wild-type and N-ras knockout mice with 3-methylcholanthrene (MCA) to induce fibrosarcomas and found that MCA is more carcinogenic in wild-type mice than in knockout mice. After injecting different doses of a tumorigenic cell line, the wild-type mice exhibited a shorter latency of tumor development than the knockouts, indicating that there are N-ras-dependent differences in the stromal cells. Likewise, we have analyzed B-cell lymphomas induced by either N-methylnitrosourea (MNU) or by the N-ras oncogene in mice that overexpress the N-ras proto-oncogene and found that the overexpression of wild-type N-ras is able to increase the incidence of these lymphomas. Considered together, our results indicate that Ras proto-oncogenes can enhance or inhibit the malignant phenotype in vivo in different systems.
Complex effects of Ras proto-oncogenes in tumorigenesis
2 Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461
3 Endocrinology Research Unit, Joan XXIII University Hospital, Rovira i Virgili University School of Medicine, Dr. Mallafre i Guasch 4, Tarragona, Spain
4 Laboratori d'Investigació Gastrointestinal, Institut de Recerca, Hospital de Sant Pau, 08025 Barcelona, Spain
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Modrek, L. Ge, A. Pandita, E. Lin, S. Mohan, P. Yue, S. Guerrero, W. M. Lin, T. Pham, Z. Modrusan, et al. Oncogenic Activating Mutations Are Associated with Local Copy Gain Mol. Cancer Res., August 1, 2009; 7(8): 1244 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-I. Kwak, T. Gustafson, R. P. Metz, B. Laffin, P. Schedin, and W. W. Porter Inhibition of breast cancer growth and invasion by single-minded 2s Carcinogenesis, February 1, 2007; 28(2): 259 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Sundaram The love-hate relationship between Ras and Notch Genes & Dev., August 15, 2005; 19(16): 1825 - 1839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Singh, A. P. Sowjanya, and G. Ramakrishna The wild-type Ras: road ahead FASEB J, February 1, 2005; 19(2): 161 - 169. [Abstract] [Full Text] [PDF]
|
|