Suppression of a human colon cancer cell line by introduction of an exogenous NF1 gene.
Suppression of a human colon cancer cell line by introduction of an exogenous NF1 gene.
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通过引入外源 NF1 基因抑制人结肠癌细胞系。
作者：
Y. Li;Raymond White
人结肠癌细胞系HCT116含有一个致癌基因Ki-ras。引入外源性全长NF1基因或其gtpase激活蛋白（GAP）相关结构域可抑制裸鼠该细胞系的肿瘤形成能力。我们还测试了一个携带K1423E突变的GAP相关结构域肽，该肽显示GAP活性大大降低，但与p2lras-GTP具有正常的结合亲和力。该构建体能够抑制HCT116细胞系的肿瘤形成，从而排除了观察到的肿瘤抑制是由于NF1的GAP活性所致的可能性。在表达这些NF1结构的细胞中，Raf-1激酶活性降低表明神经纤维蛋白可能干扰Ras和Raf之间的相互作用。引入突变激活的Raf-1激酶结构域逆转了神经纤维蛋白对肿瘤的抑制，暗示Raf-1是致癌Ras信号的主要下游换能器。在携带外源性NF1基因的细胞中，凋亡细胞死亡的增加，可以通过活化的Raf-1激酶延迟。
Human colon carcinoma cell line HCT116 harbors an oncogenic Ki-ras gene. Introduction of an exogenous full-length NF1 gene or its GTPase-activating protein (GAP)-related domain suppressed the tumor-forming ability of this cell line in nude mice. A GAP-related domain peptide carrying a K1423E mutation, which shows greatly diminished GAP activity but a normal binding affinity for p2lras-GTP, was also tested. This construct was able to suppress tumor formation by the HCT116 cell line, thus ruling out the possibility that the observed tumor suppression is due to the GAP activity of NF1. Reduced Raf-1 kinase activity in cells which expressed these NF1 constructs suggested that neurofibromin may interfere with the interaction between Ras and Raf. Introduction of a mutationally activated Raf-1 kinase domain reversed tumor suppression by neurofibromin, implicating Raf-1 as the primary downstream transducer of the oncogenic Ras signal. An increase in apoptotic cell death, which could be delayed by activated Raf-1 kinase, was also seen in cells carrying the exogenous NF1 gene.
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影响因子：
8
作者：
Hong-Gang Wang;T. Miyashita;S. Takayama;T. Sato;T. Torigoe;S. Krajewski;S. Tanaka;Hovey L rd;J. Troppmair;U. Rapp
通讯作者：
Hong-Gang Wang;T. Miyashita;S. Takayama;T. Sato;T. Torigoe;S. Krajewski;S. Tanaka;Hovey L rd;J. Troppmair;U. Rapp
影响因子：
56.9
作者：
MOODIE, SA;WILLUMSEN, BM;WOLFMAN, A
通讯作者：
WOLFMAN, A
神经纤维蛋白的催化特性、组织和细胞内分布。
影响因子：
8
作者：
Golubic,M;Roudebush,M;Dobrowolski,S;Wolfman,A;Stacey,DW
通讯作者：
Stacey,DW
DOI：
10.1073/pnas.90.12.5539
发表时间：
1993-06-15
影响因子：
11.1
作者：
JOHNSON, MR;LOOK, AT;LOWY, DR
通讯作者：
LOWY, DR
影响因子：
56.9
作者：
SU, LK;VOGELSTEIN, B;KINZLER, KW
通讯作者：
KINZLER, KW