Krajci P, Meling G I, Andersen S N, Hofstad B, Vatn M H, Rognum T O, Brandtzaeg P
Laboratory for Immunohistochemisty and Immunopathology (LIIPAT), Institute of Pathology, Rikshospitalet, University of Oslo, Norway.
Br J Cancer. 1996 Jun;73(12):1503-10. doi: 10.1038/bjc.1996.284.
Secretary component (SC) is expressed basolaterally as a transmembrane protein (pIg receptor) on secretory epithelial cells. As pIg receptor it plays a central role in humoral immunity by mediating the external translocation of dimeric IgA and pentameric IgM. A few case reports have suggested that reduced or absent SC protein expression is associated with diarrhoeal disease, but there is no convincing evidence that a primary pIg receptor deficiency can occur. In this study the relative presence of SC mRNA was determined by Northern blot analysis and related to immunohistochemically determined SC protein expression in 33 colorectal adenomas (31 patients) with increased risk of developing sporadic colorectal cancer, as well as in 19 colorectal carcinomas from 19 patients with such sporadic tumours. In the adenomas, SC mRNA levels were positively related to SC protein expression; both mRNA and SC protein were negatively related to histological grade. Similarly, SC mRNA levels tended to be related to the SC protein expression in the carcinomas. SC mRNA was detected in all adenomas, and only two of ten carcinomas (10.5%) deemed to be SC deficient by immunohistochemistry also lacked SC mRNA expression, suggesting diallelic alterations in the SC-encoding gene (locus PIGR). This possibility agreed with Southern blot analysis performed on a separate sample of 32 other colonic carcinomas in which the diallelic loss of D1S58 (which exhibits a close linkage centromerically to PIGR) was calculated to be 6.4%. Together these findings suggested that reduced SC protein expression in colorectal adenomas might be a transcriptional defect reflecting the degree of cellular dysplasia, whereas absent SC protein expression in colorectal carcinomas might also involve post-transcriptional defects and occasional diallelic gene deletions representing late events in carcinogenesis.
分泌成分（SC）作为跨膜蛋白（多聚免疫球蛋白受体）在分泌上皮细胞的基底外侧表达。作为多聚免疫球蛋白受体，它通过介导二聚体IgA和五聚体IgM的外向转运在体液免疫中发挥核心作用。一些病例报告表明，SC蛋白表达降低或缺失与腹泻病有关，但没有令人信服的证据表明会发生原发性多聚免疫球蛋白受体缺乏症。在本研究中，通过Northern印迹分析确定了SC mRNA的相对存在情况，并将其与33例有散发性结直肠癌发生风险增加的结直肠腺瘤（31例患者）以及19例患有此类散发性肿瘤的患者的19例结直肠癌中免疫组织化学测定的SC蛋白表达相关联。在腺瘤中，SC mRNA水平与SC蛋白表达呈正相关；mRNA和SC蛋白均与组织学分级呈负相关。同样，SC mRNA水平在癌中也倾向于与SC蛋白表达相关。在所有腺瘤中均检测到SC mRNA，在通过免疫组织化学被认为SC缺乏的10例癌中只有2例（10.5%）也缺乏SC mRNA表达，提示SC编码基因（基因座PIGR）存在双等位基因改变。这种可能性与对另外32例结肠癌的单独样本进行的Southern印迹分析结果一致，在该分析中计算出D1S58（其在着丝粒方向与PIGR紧密连锁）的双等位基因缺失率为6.4%。这些发现共同表明，结直肠腺瘤中SC蛋白表达降低可能是反映细胞发育异常程度的转录缺陷，而结直肠癌中SC蛋白表达缺失可能还涉及转录后缺陷以及偶尔的双等位基因缺失，这些代表了致癌过程中的晚期事件。
