RAS-MEDIATED CELL-CYCLE ARREST IS ALTERED BY NUCLEAR ONCOGENES TO INDUCE SCHWANN-CELL TRANSFORMATION
RAS-MEDIATED CELL-CYCLE ARREST IS ALTERED BY NUCLEAR ONCOGENES TO INDUCE SCHWANN-CELL TRANSFORMATION
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DOI：
10.1002/j.1460-2075.1988.tb02990.x
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发表时间：
1988-06-01
期刊：
影响因子：
11.4
通讯作者：
LAND, H
中科院分区：
文献类型：
--
作者：
RIDLEY, AJ;PATERSON, HF;LAND, H
在纯化的大鼠雪旺细胞群中研究了细胞反应t ras和核癌基因。v-HA-ras和SV 40大T协同转化雪旺细胞，在软琼脂中诱导生长并允许在不添加有丝分裂原的情况下增殖。单独表达大T减少了它们对生长因子的需求，但不足以诱导完全转化。与此相反，V-Ha-ras的表达导致雪旺氏细胞增殖停滞，在限制性温度下表达大T的温度敏感突变体。细胞停滞在细胞周期的G1或G2/M期，并且即使在限制性条件下长时间之后，也可以在允许温度下重新进入细胞分裂。当显微注射到雪旺细胞中时，致癌ras蛋白也抑制DNA合成。腺病毒E1 a和c-myc癌基因的行为与SV 40大T相似。它们与Ha-ras癌基因合作转化雪旺细胞，并防止ras诱导的生长停滞。因此，核癌基因从根本上改变了雪旺细胞对ras癌基因的反应，从细胞周期停滞到转化。
The cellular responses t ras and nuclear oncogenes were investigated in purified populations of rat Schwann cells. v-HA-ras and SV40 large T cooperate to transform Schwann cells, inducing growth in soft agar and allowing proliferation in the absence of added mitogens. Expression of large T alone reduces their growth factor requirements but is insufficient to induce full transformation. In contrast, expression of V-Ha-ras leads to proliferation arrest in Schwann cells expressing a temperature-sensitive mutant of large T at the restrictive temperature. Cells arrest in either the G1 or G2/M phases of the cell cycle, and can re-enter cell division at the permissive temperature even after prolonged periods at the restrictive conditions. Oncogenic ras proteins also inhibit DNA synthesis when microinjected into Schwann cells. Adenovirus E1a and c-myc oncogenes behave similarly to SV40 large T. They cooperate with Ha-ras oncogenes to transform Schwann cells, and prevent ras-induced growth arrest. Thus nuclear oncogenes fundamentally alter the response of Schwann cells to a ras oncogene from cell cycle arrest to transformation.