Ashida Reiko, Tominaga Kazunari, Sasaki Eiji, Watanabe Toshio, Fujiwara Yasuhiro, Oshitani Nobuhide, Higuchi Kazuhide, Mitsuyama Shokei, Iwao Hiroshi, Arakawa Tetsuo
Department of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Inflammopharmacology. 2005;13(1-3):113-25. doi: 10.1163/156856005774423935.
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.
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。
