Induction of apoptosis in NIH3T3 cells after serum deprivation by overexpression of rho-p21, a GTPase protein of the ras superfamily.
Oncogenes appear to influence apoptosis in two ways. Some activate cells from a growth-arrested state to one in which both apoptosis and entry to S-phase become possible, the choice between them being determined by a second signal, such as cytokine or growth factor. Cells in this state are often sensitive to apoptosis induced by a wide variety of agents, including several drugs used in cancer chemotherapy. Other oncogenes prevent activation of the apoptosis effector pathway, even in the presence of a death stimulus, the affected cells therefore being resistant to chemotherapeutic agents. In rodent fibroblasts, c-myc or the adenovirus oncogene E1A effect the first type of change, whereas bcl-2, v-abl, E1B or activated ras effect the second. Here we study in rodent fibroblast the effect of expression of rho genes, members of the ras superfamily which we have previously shown to be tumorigenic when highly expressed in this cell type. We show that expression of wild-type rho from Aplysia californica stimulates apoptosis in cultured cell lines and that the apoptotic index in tumors generated by these cell lines is similar to those induced by E1A-transformed cells. In contrast, mutated rho, activated by Val14 substitution in the GTP binding site, it less potent as a stimulator of apoptosis, generating a phenotype more similar to that obtained with activated ras. Thus, rho genes may play a critical role in the regulation of apoptosis.
Jiménez
B
B
Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.
Arends
M
M
Esteve
P
P
Perona
R
R
Sánchez
R
R
Ramón y Cajal
S
S
Wyllie
A
A
Lacal
J C
JC
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D002945:Cisplatin / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D004247:DNA / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D051379:Mice; D014162:Transfection; D020741:rho GTP-Binding Proteins
D016895:Culture Media, Serum-Free; D004247:DNA; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D002945:Cisplatin