Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer.
Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer.
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野生型 p21Ras 的过度表达在结直肠癌中发挥着重要作用
DOI：
10.3892/ijmm.2017.2903
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发表时间：
2017-04
影响因子：
5.4
通讯作者：
Yang JL
中科院分区：
文献类型：
--
作者：
Bai S;Feng Q;Pan XY;Zou H;Chen HB;Wang P;Zhou XL;Hong YL;Song SL;Yang JL
结直肠癌（CRC）是最常见的胃肠道癌症。 Ras 蛋白（尤其是 p21Ras）的过度表达与 CRC 的发生有关。然而，过表达的p21Ras蛋白的亚型和突变状态仍然未知，限制了针对p21Ras蛋白的治疗性抗体的开发。本研究旨在调查与 CRC 中过度表达的 Ras 蛋白相关的 ras 基因的突变状态，并探讨野生型 p21Ras 是否可以作为 CRC 治疗的靶点。使用单克隆抗体 (Mab) KGH-R1 对正常结直肠上皮、良性病变和恶性结直肠肿瘤组织中的 p21Ras 表达进行免疫组织化学检查，该单克隆抗体 (Mab) KGH-R1 能够与三种类型的 p21Ras 蛋白发生反应：H-p21Ras、N-p21Ras 和 K-p21Ras。然后，通过每种 p21Ras 亚型的特定 Mab 测定 CRC 中 p21Ras 亚型的表达水平。通过DNA测序检测p21Ras过表达CRC中ras基因的突变状态。正常结直肠上皮中 p21Ras 表达很少，但结直肠癌中 p21Ras 表达水平较高，并且从正常结直肠上皮到炎性息肉、低度上皮内瘤变、高度上皮内瘤变和浸润性结直肠腺癌分别显着增加。所有结直肠癌组织中均发现K-p21Ras过表达，85.7%的结直肠癌组织中发现N-p21Ras过表达，而所有结直肠癌组织中均未发现H-p21Ras表达。 DNA测序显示，60%的K-p21Ras过表达CRC组织中没有K-ras突变，而40%的CRC组织含有K-ras突变。在任何 N-p21Ras 过表达的 CRC 中均未发现 N-ras 突变。我们的研究结果表明，除了 ras 突变之外，野生型 p21Ras 的过度表达可能在 CRC 的发展中发挥着重要作用，并且可能成为 CRC 治疗的有希望的靶点。
Colorectal cancer (CRC) is the most common gastrointestinal type of cancer. The overexpression of Ras proteins, particularly p21Ras, are involved in the development of CRC. However, the subtypes of the p21Ras proteins that are overexpressed and the mutation status remain unknown restricting the development of therapeutic antibodies targeting p21Ras proteins. The present study aimed to investigate the mutation status of ras genes associated with Ras proteins that are overexpressed in CRC and explore whether or not wild-type p21Ras could be a target for CRC therapy. p21Ras expression was examined immunohistochemically in normal colorectal epithelium, benign lesions and malignant colorectal tumor tissues by monoclonal antibody (Mab) KGH-R1 which is able to react with three types of p21Ras proteins: H-p21Ras, N-p21Ras and K-p21Ras. Then, the expression levels of p21Ras subtypes were determined in CRC by a specific Mab for each p21Ras subtype. Mutation status of ras genes in p21Ras-overexpressing CRC was detected by DNA sequencing. There was rare p21Ras expression in normal colorectal epithelium but a high level of p21Ras expression in CRC, with a significant increase from normal colorectal epithelium to inflammatory polyps, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and invasive colorectal adenocarcinoma, respectively. Overexpression of K-p21Ras was found in all CRC tissues tested, overexpression of N-p21Ras was found in 85.7% of the CRC tissues, while H-p21Ras expression was not found in any CRC tissue. DNA sequencing showed that there were no K-ras mutations in 60% of the K-p21Ras-overexpressing CRC, while 40% of the CRC tissues harbored K-ras mutations. N-ras mutations were not found in any N-p21Ras-overexpressing CRC. Our findings indicate that overexpression of wild-type p21Ras may play a prominent role in the development of CRC in addition to ras mutations and could be a promising target for CRC therapy.
影响因子：
8.8
作者：
Scambia, G;Catozzi, L;Benedetti Panici, P;Ferrandina, G;Almadori, G;Paludetti, G;Cadoni, G;Distefano, M;Piffanelli, A;Mancuso, S
通讯作者：
Mancuso, S
DOI：
10.1084/jem.161.5.1213
发表时间：
1985-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Viola MV;Fromowitz F;Oravez S;Deb S;Schlom J
通讯作者：
Schlom J