Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo
Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo
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DOI：
10.1038/sj.cgt.7700126
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发表时间：
2000-03-01
影响因子：
6.4
通讯作者：
Ilan, J
中科院分区：
文献类型：
--
作者：
Chernicky, CL;Yi, LJ;Ilan, J
I型胰岛素样生长因子受体（IGF-IR）在乳腺癌细胞的生长和转化中发挥着重要作用。在这项研究中，我们研究了反义 ICF-IR 构建体治疗对高度转移性雌激素受体阴性人乳腺癌细胞系 MDA-MB-435s 细胞的影响。携带反义IGF-IR的细胞的ICF-IR表达显着降低，细胞增殖显着降低，并且失去在分选琼脂中形成集落的能力。当携带反义 ICF-IR 的细胞注射到裸鼠或严重联合免疫缺陷 (scid) 米色小鼠中时，肿瘤形成延迟，肿瘤大小显着减小。我们还提供的数据表明，scid 米色小鼠是更适合研究 MDA-MB-435s 细胞转移的模型。所有注射携带对照构建体的细胞的 scid 米色小鼠均出现肺部转移，而裸鼠的肺部在 11 周后没有明显的转移部位。当将携带反义 IGF-IR 的细胞皮下注射到 scid 米色小鼠体内时，与注射携带对照构建体的细胞的小鼠相比，这些动物的存活率显着增加。综上所述，这些结果表明 IGF-IR 在乳腺癌的进展中发挥着关键作用。我们的研究为未来针对转移性乳腺癌的 GF-IR 治疗策略的开发提供了基础。
The type I insulin-like growth Factor receptor (IGF-IR) plays an important role in the growth and transformation of breast cancer cells. In this study, we investigated the effects of treatment with an antisense ICF-IR construct on cells from the highly metastatic estrogen receptor-negative human breast cancer cell line MDA-MB-435s. The cells carrying the antisense IGF-IR had a markedly reduced expression of ICF-IR, had a significant decrease in cell proliferation, and lost the ability to form colonies in sort agar. There was a delay in tumor formation and a dramatic reduction in tumor size when cells carrying the antisense ICF-IR were injected into either nude or severe combined immunodeficient (scid) beige mice. We have also provided data that show that the scid beige mouse is a more suitable model for studying metastasis of the MDA-MB-435s cells. All of the scid beige mice injected with cells carrying the control construct had metastasis to the lungs, whereas lungs from the nude mice had no apparent metastatic sites after 11 weeks. When cells carrying antisense IGF-IR were injected subcutaneously in scid beige mice, the animals had a significant increase in survival compared with mice injected with cells carrying the control construct. Taken together, these results indicate that the IGF-IR can play a critical role in the progression of breast cancer. Our studies provide a basis for the development of future treatment strategies targeting the]GF-IR in metastatic breast cancer.