Calzolari Alessia, Deaglio Silvia, Maldi Elena, Cassoni Paola, Malavasi Fabio, Testa Ugo
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Blood Cells Mol Dis. 2009 Nov-Dec;43(3):243-9. doi: 10.1016/j.bcmd.2009.08.001. Epub 2009 Sep 2.
Different proteins regulate iron metabolism at the level of various tissues. Among these is a second transferrin receptor (TfR2) that seems to play a key role in the regulation of iron homeostasis. Although TfR2 expression in normal tissues is restricted at the level of the liver, we observed that TfR2 is frequently expressed in cancer cell lines. Taking advantage of this observation we investigated TfR2 expression in primary colon cancers, and showed that this receptor is expressed in about 26% of cases. TfR2 expression in colon cancer is not related to histological grade, but is preferentially associated with mucinous tumors. In colon cancer cell lines, TfR2 is localized in membrane lipid rafts, induces ERK1/ERK2 phosphorylation, when activated by its ligand transferring, and is preferentially expressed during S-M phases of the cell cycle. The presence of TfR2 on the membrane of colon cancer cells may contribute the growth advantage to these cells.
不同的蛋白质在各种组织水平上调节铁代谢。其中有一种第二种转铁蛋白受体(TfR2),它似乎在铁稳态调节中起关键作用。尽管TfR2在正常组织中的表达在肝脏水平受到限制,但我们观察到TfR2在癌细胞系中经常表达。利用这一观察结果,我们研究了原发性结肠癌中TfR2的表达,并表明该受体在约26%的病例中表达。结肠癌中TfR2的表达与组织学分级无关,但优先与黏液性肿瘤相关。在结肠癌细胞系中,TfR2定位于膜脂筏,当被其配体转铁蛋白激活时诱导ERK1/ERK2磷酸化,并且在细胞周期的S-M期优先表达。结肠癌细胞膜上TfR2的存在可能赋予这些细胞生长优势。