Yoshioka Akiko, Miyata Hiroshi, Doki Yuichiro, Yamasaki Makoto, Sohma Itsuro, Gotoh Kunihito, Takiguchi Shuji, Fujiwara Yoshiyuki, Uchiyama Yasuo, Monden Morito
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Int J Oncol. 2008 Sep;33(3):461-8.
Autophagy is a bulk protein and organelle degradation process essential for cell maintenance and viability. Microtubule-associated protein 1 light chain 3 (LC3), the mammalian homologue of yeast Atg8, is involved in autophagosome formation during autophagy. The aim of this study was to investigate LC3 expression in gastrointestinal cancers to elucidate the role of autophagy in human cancer development. We evaluated LC3 expression by immunohistochemistry in 163 gastrointestinal cancers including 106 esophageal, 38 gastric and 19 colorectal cancers. Seventy precancerous intraepithelial neoplasias were found in esophageal cancer specimens. LC3 expression was compared with Ki-67 staining and expression of carbonic anhydrase (CA) IX, a hypoxic marker. LC3 was expressed in the cytoplasm of cancer cells, but not in noncancerous epithelial cells. A high expression of LC3 was observed in 53% of esophageal, 58% of gastric and 63% of colorectal cancers. LC3 immunoreactive score gradually increased during early esophageal carcinogenesis in low- and high-grade intraepithelial neoplasia and T1 carcinoma, while it did not change in later cancer progression (T2-T4 carcinomas). In early esophageal carcinogenesis, LC3 expression correlated with Ki-67 labeling index (p=0.0001), but showed no significant association with CAIX expression. In esophageal cancers, LC3 expression did not correlate with various clinicopathological factors, including survival. LC3 is upregulated in various gastrointestinal cancers and partly associated with Ki-67 index. Our results suggest that LC3 expression is advantageous to cancer development especially in early-phase carcinogenesis.
自噬是一种大量蛋白质和细胞器降解过程，对细胞维持和生存至关重要。微管相关蛋白1轻链3（LC3）是酵母Atg8的哺乳动物同源物，在自噬过程中参与自噬体形成。本研究的目的是调查胃肠道癌症中LC3的表达，以阐明自噬在人类癌症发生中的作用。我们通过免疫组织化学评估了163例胃肠道癌症中LC3的表达，其中包括106例食管癌、38例胃癌和19例结直肠癌。在食管癌标本中发现了70例癌前上皮内瘤变。将LC3表达与Ki-67染色以及缺氧标志物碳酸酐酶（CA）IX的表达进行比较。LC3在癌细胞的细胞质中表达，但在非癌上皮细胞中不表达。在53%的食管癌、58%的胃癌和63%的结直肠癌中观察到LC3高表达。在低级别和高级别上皮内瘤变以及T1期癌的早期食管癌发生过程中，LC3免疫反应评分逐渐增加，而在后期癌症进展（T2-T4期癌）中则没有变化。在早期食管癌发生过程中，LC3表达与Ki-67标记指数相关（p=0.0001），但与CAIX表达无显著关联。在食管癌中，LC3表达与包括生存在内的各种临床病理因素无关。LC3在各种胃肠道癌症中上调，且部分与Ki-67指数相关。我们的结果表明，LC3表达有利于癌症发展，尤其是在早期致癌过程中。
