The N-ras proto-oncogene can suppress the malignant phenotype in the presence or absence of its oncogene.
ras proto-oncogenes have traditionally been associated with the regulation and promotion of cell growth. We have induced thymic lymphomas in N-ras(-/-) mice and in transgenic mice that overexpress wild-type N-ras and found that the lack of wild-type N-ras alleles favors the development of thymic lymphomas,whereas overexpression of wild-type N-ras protects against thymic lymphomagenesis in the presence or absence of its oncogene. To investigate the inhibitory role of wild-type N-ras in in vitro transformation, we introduced wild-type N-ras in N-ras-deficient tumor cells that lack ras activating mutations and found decreased growth in both low serum and soft agar. Taken together, our results indicate that wild-type N-ras has "tumor suppressor" activity, even in the absence of its oncogenic allele.
Diaz
Roberto
R
Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA.
Ahn
Daniel
D
Lopez-Barcons
Lluis
L
Malumbres
Marcos
M
Perez de Castro
Ignacio
I
Lue
Jeffrey
J
Ferrer-Miralles
Neus
N
Mangues
Ramon
R
Tsong
Jerry
J
Garcia
Roberto
R
Perez-Soler
Roman
R
Pellicer
Angel
A
D000483:Alleles; D000818:Animals; D003433:Crosses, Genetic; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008223:Lymphoma / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013953:Thymus Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics
D018631:ras Proteins