Wildi S, Kleeff J, Maruyama H, Maurer C A, Büchler M W, Korc M
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of California, Irvine, California, USA.
Gut. 2001 Sep;49(3):409-17. doi: 10.1136/gut.49.3.409.
Activins and inhibins are dimeric polypeptides that belong to the transforming growth factor beta (TGF-beta) superfamily and that bind to transmembrane receptors with serine/threonine kinase activity. The aim of this study was to characterise, in colon cancer cell lines and in normal and malignant human colon tissues, levels of expression of inhibin subunits that are involved in activin/inhibin dimer formation, and of the type I and II activin receptors (actRI and actRII).
Expression of inhibin subunits and activin receptors was analysed by northern blot analysis. Inhibin betaA and activin receptor expression were also assessed by use of polymerase chain reaction (PCR). In addition, activin A/inhibin betaA localisation in human colon samples was assessed by immunohistochemistry and in situ hybridisation.
Inhibin betaA mRNA was expressed in CaCo2 cells but not in SW 837 or SW 1463 cells whereas inhibin betaB and inhibin alpha were below the level of detection. In contrast, all four activin receptors were present in the three cell lines. Colon cancers overexpressed inhibin betaA mRNA in comparison with normal colon, and this overexpression was greatest in stage IV tumours. ActRIb mRNA levels were slightly higher in the normal colon than in cancer tissues. By immunohistochemistry and in situ hybridisation, activin A and inhibin betaA mRNA were present in the mucosal epithelial cells in normal tissues from patients with stage I disease but were either absent or weakly present in normal tissues from patients with stage IV disease. Conversely, they were present at weak to moderate levels in stage I cancers but at high levels in stage IV cancers.
Our findings indicate that activin A is overexpressed in human colorectal tumours, especially in stage IV disease, raising the possibility that activin A may have a role in advanced colorectal cancer.
激活素和抑制素是二聚体多肽，属于转化生长因子β（TGF-β）超家族，可与具有丝氨酸/苏氨酸激酶活性的跨膜受体结合。本研究旨在对参与激活素/抑制素二聚体形成的抑制素亚基以及I型和II型激活素受体（激活素受体I和激活素受体II）在结肠癌细胞系以及正常和恶性人结肠组织中的表达水平进行表征。
通过Northern印迹分析来检测抑制素亚基和激活素受体的表达。还利用聚合酶链反应（PCR）评估抑制素βA和激活素受体的表达。此外，通过免疫组织化学和原位杂交来评估激活素A/抑制素βA在人结肠样本中的定位。
抑制素βA mRNA在CaCo2细胞中表达，但在SW 837或SW 1463细胞中未表达，而抑制素βB和抑制素α低于检测水平。相比之下，三种细胞系中均存在所有四种激活素受体。与正常结肠相比，结肠癌中抑制素βA mRNA过表达，且这种过表达在IV期肿瘤中最为明显。激活素受体Ib mRNA水平在正常结肠中略高于癌组织。通过免疫组织化学和原位杂交发现，I期疾病患者正常组织的黏膜上皮细胞中存在激活素A和抑制素βA mRNA，但IV期疾病患者正常组织中不存在或仅微弱存在。相反，它们在I期癌症中呈弱至中度水平，而在IV期癌症中呈高水平。
我们的研究结果表明，激活素A在人结直肠癌中过表达，尤其是在IV期疾病中，这增加了激活素A可能在晚期结直肠癌中发挥作用的可能性。
