17β-Estradiol responsiveness of MCF-7 laboratory strains is dependent on an autocrine signal activating the IGF type I receptor
17β-Estradiol responsiveness of MCF-7 laboratory strains is dependent on an autocrine signal activating the IGF type I receptor
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DOI：
10.1186/1475-2867-3-10
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发表时间：
2003-01-01
影响因子：
5.8
通讯作者：
Steenbergh, Paul H.
中科院分区：
文献类型：
--
作者：
Hamelers, Irene Hl;van Schaik, Richard F. M. A.;Steenbergh, Paul H.
背景：人MCF-7细胞作为乳腺癌细胞生长的模型已被广泛研究。许多报道已经证实，血清饥饿的MCF-7细胞可以在单独加入17 β-雌二醇（E2）后诱导增殖。然而，对E2的促有丝分裂反应的程度在不同的MCF-7菌株中不同，甚至可能不存在。结果：MCF-7S株对E2无反应，MCF-7 ATCC株对E2有中等反应，而MCF-7 NKI株对E2高度敏感，但雌激素受体（ER）水平和活性无显著差异。苏拉明和IGF I型受体阻断抗体均能够抑制MCF-7 ATCC和MCF-7 NKI细胞对E2处理的促有丝分裂反应。从这一点，我们得出结论，E2诱导的增殖是依赖于IGF I型受体的激活在所有三个MCF-7 strain.Conclusions：本文中提出的结果表明，E2的MCF-7细胞的反应是依赖于一个自分泌因子的分泌激活IGF-IR. All三个菌株的MCF-7乳腺癌细胞调查不响应E2，如果IGF-RI通路被阻断。一般来说，乳腺癌治疗的目标是抑制雌激素的作用。这项研究表明，抑制IGF作用与抗雌激素治疗相结合，可能会提供一个更有效的方法在治疗甚至预防乳腺癌。
Background: Human MCF-7 cells have been studied extensively as a model for breast cancer cell growth. Many reports have established that serum-starved MCF-7 cells can be induced to proliferate upon the sole addition of 17 beta-estradiol (E2). However, the extent of the mitogenic response to E2 varies in different MCF-7 strains and may even be absent. In this study we compared the E2-sensitivity of three MCF-7 laboratory strains.Results: The MCF-7S line is non-responsive to E2, the MCF-7 ATCC has an intermediate response to E2, while the MCF-7 NKI is highly E2-sensitive, although the levels and activities of the estrogen receptor (ER) are not significantly different. Both suramin and IGF type I receptor blocking antibodies are able to inhibit the mitogenic response to E2-treatment in MCF-7 ATCC and MCF-7 NKI cells. From this we conclude that E2-induced proliferation is dependent on IGF type I receptor activation in all three MCF-7 strains.Conclusions: The results presented in this article suggest that E2-responsiveness of MCF-7 cells is dependent on the secretion of an autocrine factor activating the IGF-IR. All three strains of MCF-7 breast cancer cells investigated do not respond to E2 if the IGF-RI-pathway is blocked. Generally, breast cancer therapy is targeted at inhibiting estrogen action. This study suggests that inhibition of IGF-action in combination with anti-estrogen-treatment may provide a more effective way in treatment or even prevention of breast cancer.