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AP-1与结直肠癌

AP-1 and colorectal cancer.

作者信息

Ashida Reiko, Tominaga Kazunari, Sasaki Eiji, Watanabe Toshio, Fujiwara Yasuhiro, Oshitani Nobuhide, Higuchi Kazuhide, Mitsuyama Shokei, Iwao Hiroshi, Arakawa Tetsuo

机构信息

Department of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.

出版信息

Inflammopharmacology. 2005;13(1-3):113-25. doi: 10.1163/156856005774423935.

Abstract

Activator protein-1 (AP-1) is a transcription factor that consists of either a Jun-Jun homodimer or a Jun-Fos heterodimer. AP-1 regulates the expression of multiple genes essential for cell proliferation, differentiation and apoptosis. Numerous reports suggest that AP-1 plays an important role in various human diseases. Among them, the roles relating to human cancers have been strongly suggested for a long time. In human cancers, colorectal cancer is still a leading cause of morbidity and mortality in the world. Since there are some reports about the role of AP-1 in colorectal cancer response to a number of stimuli, such as cytokines and growth factors, and oncogenictransformation, therapeutic inhibition of AP-1 activity has attracted considerable interest. Here, we demonstrate the biological properties of AP-1 and its role in colorectal cancer, and discuss a possibility of an AP-1 inhibitor, an adenovirus dominant-negative mutant of c-Jun, as a therapeutic agent for gene therapy.

摘要

活化蛋白-1(AP-1)是一种转录因子,由Jun-Jun同源二聚体或Jun-Fos异源二聚体组成。AP-1调节细胞增殖、分化和凋亡所必需的多个基因的表达。大量报告表明,AP-1在多种人类疾病中起重要作用。其中,与人类癌症相关的作用长期以来一直被强烈暗示。在人类癌症中,结直肠癌仍然是全球发病和死亡的主要原因。由于有一些关于AP-1在结直肠癌对多种刺激(如细胞因子和生长因子)的反应以及致癌转化中的作用的报道,对AP-1活性的治疗性抑制引起了相当大的兴趣。在这里,我们展示了AP-1的生物学特性及其在结直肠癌中的作用,并讨论了一种AP-1抑制剂,即c-Jun的腺病毒显性负性突变体,作为基因治疗的治疗剂的可能性。

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