Antisense-fos RNA causes partial reversion of the transformed phenotypes induced by the c-Ha-ras oncogene

Antisense-fos RNA causes partial reversion of the transformed phenotypes induced by the c-Ha-ras oncogene
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反义-fos RNA 导致 c-Ha-ras 癌基因诱导的转化表型部分逆转

DOI:
10.1128/mcb.10.4.1545-1555.1990
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发表时间:
1990
影响因子:
5.3
通讯作者:
Matthews O. Bradley
Matthews O. Bradley
中科院分区:
生物学2区
文献类型:
--
作者:
B. Ledwith;S. Manam;A. Kraynak;Warren W. Nichols;Matthews O. Bradley

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多项证据表明,c-fos 可能在生长调节信号转导途径中发挥 c-Ha-ras 下游的作用。我们使用反义RNA抑制c-fos基因表达,并研究了c-fos表达减少对NIH 3T3细胞中EJ c-Ha-ras癌基因诱导的表型的影响。免疫荧光染色表明,反义RNA导致血清刺激后c-fos蛋白表达量显着减少。含有反义 fos RNA 的 EJ 细胞继续过度表达 ras,并保持体外增殖能力。然而,反义fos RNA引起EJ细胞主要转化表型的部分逆转,包括恢复密度依赖性生长停滞和通过血清剥夺而静止的能力、恢复扁平形态、抑制贴壁依赖性生长以及抑制裸鼠的致瘤性。我们的结果表明,将 c-fos 表达抑制至仍支持体外增殖的水平,可阻止 ras 癌基因的转化作用;因此,它们为 c-fos 参与 ras 调节的信号转导途径提供了额外的证据。
Several lines of evidence have suggested that c-fos may act downstream from c-Ha-ras in a growth-regulatory signal transduction pathway. We used antisense RNA to inhibit c-fos gene expression and investigated the effects of diminished c-fos expression on the phenotypes induced by the EJ c-Ha-ras oncogene in NIH 3T3 cells. Immunofluorescent staining demonstrated that the antisense RNA caused a marked reduction in the amount of c-fos protein expressed following serum stimulation. EJ cells containing antisense-fos RNA continued to overexpress ras and remained capable of proliferating in vitro. However, the antisense-fos RNA caused a partial reversion of the major transformed phenotypes of EJ cells, including a restoration of both density-dependent growth arrest and the ability to be rendered quiescent by serum deprivation, a reversion to a flat morphology, inhibition of anchorage-independent growth, and inhibition of tumorigenicity in nude mice. Our results indicate that inhibition of c-fos expression, to a level still supporting in vitro proliferation, prevents the transforming effects of the ras oncogene; they thus provide additional evidence for the participation of c-fos in ras-regulated signal transduction pathways.
ras 癌基因对生长因子刺激的磷酸肌醇水解的相反作用:对血小板衍生生长因子的脱敏和对缓激肽的敏感性增强。
DOI: 10.1073/pnas.84.9.2648
发表时间: 1987
影响因子: 11.1
作者:
Parries,G;Hoebel,R;Racker,E
通讯作者: Racker,E
DOI: 10.1126/science.3130660
发表时间: 1988-05-20
期刊: SCIENCE
影响因子: 56.9
作者:
RAUSCHER, FJ;COHEN, DR;FRANZA, BR
通讯作者: FRANZA, BR
DOI: 10.1146/annurev.biochem.56.1.779
发表时间: 1987
影响因子: 16.6
作者:
M. Barbacid
通讯作者: M. Barbacid
c-fos 基因的反义 RNA:在转化细胞系中恢复密度依赖性生长停滞。
DOI: 10.1016/s0006-291x(87)80119-5
发表时间: 1987
影响因子: 3.1
作者:
Mercola,D;Rundell,A;Westwick,J;Edwards,SA
通讯作者: Edwards,SA
转染人 Ha-ras 癌基因的 C3H 10T 1/2 小鼠成纤维细胞中蛋白激酶 C 部分下调。
DOI: --
发表时间: 1988
期刊: Cancer research
影响因子: 11.2
作者:
Weyman,CM;Taparowsky,EJ;Wolfson,M;Ashendel,CL
通讯作者: Ashendel,CL