Opposing roles for the insulin-like growth factor (IGF)-II and mannose 6-phosphate (Man-6-P) binding activities of the IGF-II/Man-6-P receptor in the growth of prostate cancer cells
Opposing roles for the insulin-like growth factor (IGF)-II and mannose 6-phosphate (Man-6-P) binding activities of the IGF-II/Man-6-P receptor in the growth of prostate cancer cells
复制标题
DOI：
10.1210/en.2002-220751
复制
发表时间：
2003-03-01
期刊：
影响因子：
4.8
通讯作者：
MacDonald, RG
中科院分区：
文献类型：
--
作者：
Schaffer, BS;Lin, MF;MacDonald, RG
IGF-II/甘露糖6-磷酸（Man-6-P）受体（IGF 2 R）在不同的结合位点结合IGF-II和Man-6-P-承载配体。IGF 2 R表达和功能的分析表明，IGF 2 R表达的降低可以部分地解释随着培养物中传代次数的增加而观察到的前列腺淋巴结癌（LNCaP）人前列腺癌细胞的生长增加。然而，表达Myc标记的IGF 2 R（IGF 2 RMyc）的LNCaP细胞比用空载体转染的对照细胞增殖更快。表达不能结合IGF-II的突变IGF 2 R（IGF 2 RMyc I/T）的LNCaP细胞比载体转染的细胞和表达IGF 2 RMyc的细胞增殖更快。相反，与对照细胞相比，在PC-3人前列腺癌细胞中强制表达IGF 2 RMyc导致增殖降低。与LNCaP细胞一样，表达IGF 2 RMyc I/T的PC-3细胞比载体转染的细胞增殖更快。IGF 2 RMyc的亚细胞分布和内化细胞表面IGF-II的能力与PC-3细胞中的内源性IGF 2 R无法区分。这些数据表明，IGF 2 R的IGF-II-和Man-6-P-结合功能具有相反的活性，相对于前列腺癌细胞的生长。给定细胞类型中每种活性的大小似乎决定了IGF 2 R对细胞生长的净效应是抑制性还是刺激性。
The IGF-II/mannose 6-phosphate (Man-6-P) receptor (IGF2R) binds IGF-II and Man-6-P-bearing ligands at distinct binding sites. Analysis of IGF2R expression and function suggested that decreased IGF2R expression could partly account for the increased growth of lymph node carcinoma of the prostate (LNCaP)human prostate cancer cells observed with increasing passage in culture. However, LNCaP cells that expressed a Myc-tagged IGF2R (IGF2RMyc) proliferated more rapidly than control cells transfected with the empty vector. LNCaP cells expressing a mutant IGF2R incompetent to bind IGF-II (IGF2RMyc I/T) proliferated more rapidly than both vector-transfected cells and cells expressing the IGF2RMyc. In contrast, forced expression of IGF2RMyc in PC-3 human prostate cancer cells resulted in decreased proliferation, compared with control cells. As in LNCaP cells, PC-3 cells expressing IGF2RMyc I/T proliferated more rapidly than vector-transfected cells. The subcellular distribution and ability to internalize cell-surface IGF-II of IGF2RMyc were indistinguishable from endogenous IGF2R in PC-3 cells. These data suggest that the IGF-II- and Man-6-P-binding functions of the IGF2R have opposing activities, with respect to growth of prostate cancer cells. The magnitude of each activity in a given cell type seems to determine whether the net effect of the IGF2R on cell growth is inhibitory or stimulatory.