The level of oncogene H-Ras correlates with tumorigenicity and malignancy.
Normal bovine adrenocortical cells and some human fibroblasts can be transformed by SV40T and H-Ras in a Ras-dependent manner. We recently reported that high levels of Ras derived from 5' LTR of retrovirrus can induce highly malignant and fast growing tumors, while lower levels of Ras derived from internal ribosome entry site (IRES) promotes slower tumor growth and loss of malignancy. Ras derived from CMV promoters resulted in much lower Ras levels and loss of tumor malignancy and growth. Further studies showed that the tumors formed in the presence of lower levels of Ras and dominant negative P53 (P53DD) had fewer apoptotic cells and grew faster than the tumors formed from cells with same level Ras and SV40T. Our studies suggest that low levels of Ras are insufficient to inhibit apoptosis induced by pRb inactivation. In contrast, high levels of Ras not only allow normal cells to exit senescence and form tumors, but also protect against pRb inhibition-induced cell apoptosis.
Sun
Beicheng
B
Liver Transplantation Center of the First Affiliated Hospital and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, P.R.China. sunbc@njmu.edu.cn
Gao
Yun
Y
Deng
Lei
L
Li
Guoqiang
G
Cheng
Feng
F
Wang
Xuehao
X
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002417:Cattle; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D012190:Retroviridae