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人胃和结肠中DNA片段化因子的免疫组织化学:其与细胞凋亡的相关性。

Immunohistochemistry of DNA fragmentation factor in human stomach and colon: its correlation to apoptosis.

作者信息

Sasaki H, Suzuki T, Funaki N, Hoshi T, Iwabuchi M, Ohi R, Sasano H

机构信息

Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.

出版信息

Anticancer Res. 1999 Nov-Dec;19(6B):5277-82.

PMID:10697549
Abstract

DNA fragmentation factor (DFF) is an important factor in the pathway leading to apoptosis, which is activated by caspase-3 and is involved in the formation of nuclear DNA fragments. DFF is a heterodimic protein of 40kDa and 45kDa that becomes activated when DFF is cleaved by caspase-3. Of the two enzymatically cleaved fragments of DFF, it is the 40kDa fragment (DFF40) that is the active component of DFF and is responsible for triggering chromatin condensation when incubated with nuclei. However, the topological correlation between apoptosis and DFF expression in human tissues has not been examined. Therefore, in this study, we first immunolocalized DFF in non-neoplastic mucosa, hyperplastic polyp, adenoma and carcinoma of human stomach and colon. We then examined apoptosis in serial tissue sections. Labeling index (LI) of DFF and TUNEL positive cells in the same areas of serial tissue sections were obtained using computer-assisted image analysis. In the stomach, the DFF LI in non-neoplastic mucosa (9.8 +/- 5.0%, n = 3) and carcinoma (18.2 +/- 3.6, n = 3) were significantly lower than that of hyperplastic polyp (73.3 +/- 9.2%, n = 3) and adenoma (66.5 +/- 18.3%, n = 3) [p < 0.0001]. In colon, the DFF LI in non-neoplastic mucosa (10.2 +/- 6.4%, n = 3) was significantly lower than that of hyperplastic polyp (56.0 + 34.7%, n = 3) [p = 0.0013] and adenoma (30.1 +/- 16.3%, n = 3) [p = 0.0037]. Cells positive for DFF were much more widely distributed than TUNEL positive cells in both non-pathologic and pathologic mucosa of human stomach and colon. Notably, DFF positive cells were present beneath the TUNEL positive cells in non-pathological gastric and colonic epithelium. In addition, there was a significant positive correlation between DFF and TUNEL LIs in human stomach and colon [p < 0.0001]. These results suggest that DFF may be involved in the process of apoptosis in human gastric and colonic mucosa.

摘要

DNA片段化因子(DFF)是细胞凋亡通路中的一个重要因子,它由半胱天冬酶-3激活,并参与核DNA片段的形成。DFF是一种由40kDa和45kDa组成的异源二聚体蛋白,当被半胱天冬酶-3切割时被激活。在DFF的两个酶切片段中,40kDa片段(DFF40)是DFF的活性成分,与细胞核孵育时可引发染色质凝聚。然而,人体组织中细胞凋亡与DFF表达之间的拓扑相关性尚未得到研究。因此,在本研究中,我们首先对人胃和结肠的非肿瘤性黏膜、增生性息肉、腺瘤和癌组织中的DFF进行了免疫定位。然后,我们检查了连续组织切片中的细胞凋亡情况。使用计算机辅助图像分析获得连续组织切片相同区域的DFF标记指数(LI)和TUNEL阳性细胞数。在胃组织中,非肿瘤性黏膜(9.8±5.0%,n = 3)和癌组织(18.2±3.6,n = 3)中的DFF LI显著低于增生性息肉(73.3±9.2%,n = 3)和腺瘤(66.5±18.3%,n = 3)[p < 0.0001]。在结肠组织中,非肿瘤性黏膜(10.2±6.4%,n = 3)中的DFF LI显著低于增生性息肉(56.0 + 34.7%,n = 3)[p = 0.0013]和腺瘤(30.1±16.3%,n = 3)[p = 0.0037]。在人胃和结肠的非病理性和病理性黏膜中,DFF阳性细胞的分布比TUNEL阳性细胞广泛得多。值得注意的是,在非病理性胃和结肠上皮中,DFF阳性细胞位于TUNEL阳性细胞下方。此外,人胃和结肠中DFF与TUNEL LI之间存在显著正相关[p < 0.0001]。这些结果表明,DFF可能参与人胃和结肠黏膜的细胞凋亡过程。

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