Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells
Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells
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DOI：
10.1210/me.10.3.286
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发表时间：
1996-03-01
影响因子：
--
通讯作者：
Cullen, KJ
中科院分区：
文献类型：
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作者：
Ellis, MJC;Leav, BA;Cullen, KJ
我们利用编码IGF-I、IGF-II和IGF-I的逆转录病毒，在MCF-7乳腺癌细胞中研究了胰岛素样生长因子-I受体(IGF-IR)和胰岛素样生长因子-II/甘露糖6-磷酸受体(IGF-IIR)对胰岛素样生长因子-II(IGF-II)信号的自分泌调节作用。IGF-IR亲和力是无血清增殖所必需的，但也是有效分泌IGF-II所必需的，相反，在存在IGF-IIR亲和力的情况下，细胞增殖、受体酪氨酸激酶依赖的信号转导和细胞外IGF-II蛋白积累都被降低，抑制IGF-II信号似乎是IGF-IIR亲和力降低的唯一结果，因为不能检测到可归因于通过降低的IGF-IR亲和力选择性结合IGF-IIR的细胞反应，通过作为IGF-II拮抗剂操作，IGF-IIR具有肿瘤抑制样特性，这一建议与多种人类恶性肿瘤中IGF-IIR基因杂合性丢失的报道一致。
We have investigated the autocrine regulation of insulin-like growth factor-II (IGF-II) signaling by the insulin-like growth factor-I receptor (IGF-IR) and the insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-IIR) in MCF-7 breast cancer cells, employing retroviruses encoding both IGF-I, IGF-II, and IGF-I and II mutants with reductions in affinity for either the IGF-IR or the IGF-IIR, These studies revealed reciprocal roles for IGF-IR and IGF-IIR affinity in the regulation of autocrine IGF-II activity, IGF-IR affinity was required for serum-free proliferation but also for efficient IGF-II secretion, In contrast, cellular proliferation, receptor tyrosine kinase-dependent signaling, and extracellular IGF-II protein accumulation were all reduced in the presence of IGF-IIR affinity, Inhibition of IGF-II signaling appeared to be the sole consequence of IGF-IIR affinity, as no cellular responses attributable to selective IGF-IIR binding by a reduced IGF-IR affinity IGF-II mutant could be detected, By operating as an IGF-II antagonist, the IGF-IIR has tumor suppressor-like properties, a suggestion consistent with reports of loss of heterozygosity at the IGF-IIR locus in a variety of human malignancies.