Ohno Nobuhiko, Terada Nobuo, Murata Shin-ichi, Yamakawa Hisashi, Newsham Irene F, Katoh Ryohei, Ohara Osamu, Ohno Shinichi
Department of Anatomy, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Tamaho, 409-3898 Yamanashi, Japan.
Histochem Cell Biol. 2004 Dec;122(6):579-86. doi: 10.1007/s00418-004-0716-7. Epub 2004 Oct 29.
Recently, we have reported that the protein 4.1B immunolocalization occurred only in matured columnar epithelial cells of normal rat intestines. This finding suggested that protein 4.1B expression could be examined for a possible change during neoplastic transformation of the intestinal mucosa. In the present study, we first present the distribution of mouse protein 4.1B in normal intestinal epithelial cells and tumor cells using the adenomatous polyposis coli (Apc) mutant mouse model. A low level of protein 4.1B expression coincided with the phenotypic transition to carcinoma. To examine the protein 4.1B expression in human intestinal mucosa, we used another antibody against an isoform of the human protein 4.1B, DAL-1 (differentially expressed adenocarcinoma of the lung). Human DAL-1 was also expressed in matured epithelial cells in human colons, with a definite expression gradient along the crypt axis. In human colorectal cancer cells, however, DAL-1 expression was not detected. These results suggest that mouse protein 4.1B and human DAL-1 might have a striking analogy of functions, which may be integrally involved in epithelial proliferation. We propose that loss of protein 4.1B/DAL-1 expression might be a marker of intestinal tumors, indicative of a tumor suppressor function in the intestinal mucosa.
最近,我们报道蛋白质4.1B的免疫定位仅出现在正常大鼠肠道的成熟柱状上皮细胞中。这一发现表明,可以检测蛋白质4.1B的表达,以观察肠黏膜肿瘤转化过程中可能发生的变化。在本研究中,我们首先利用腺瘤性息肉病大肠杆菌(Apc)突变小鼠模型,展示小鼠蛋白质4.1B在正常肠上皮细胞和肿瘤细胞中的分布。蛋白质4.1B的低水平表达与向癌的表型转变相一致。为了检测人肠黏膜中蛋白质4.1B的表达,我们使用了另一种针对人蛋白质4.1B的一种同工型DAL-1(肺腺癌差异表达)的抗体。人DAL-1也在人结肠的成熟上皮细胞中表达,沿隐窝轴有明确的表达梯度。然而,在人结肠癌细胞中未检测到DAL-1表达。这些结果表明,小鼠蛋白质4.1B和人DAL-1可能在功能上有显著的相似性,这可能整体参与上皮增殖。我们提出,蛋白质4.1B/DAL-1表达的缺失可能是肠肿瘤的一个标志物,表明其在肠黏膜中具有肿瘤抑制功能。