GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells.
GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells.
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DOI：
10.1186/1471-2407-11-231
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发表时间：
2011-06-09
期刊：
影响因子：
3.8
通讯作者：
Serrero G
中科院分区：
文献类型：
--
作者：
Abrhale T;Brodie A;Sabnis G;Macedo L;Tian C;Yue B;Serrero G
通过阻断雌激素合成抑制乳腺癌细胞生长的芳香酶抑制剂（AI）已成为绝经后雌激素受体阳性（ER+）乳腺癌妇女的治疗选择。然而，一些患者表现出对AI的新发或获得性耐药性。雌激素和生长因子信号通路之间的相互作用已被确定为一个可能的原因，在雌激素反应细胞获得的阻力。我们的实验室已经描述了一种在浸润性导管癌中过表达的自分泌生长因子，称为PC细胞衍生生长因子（GP 88），也称为颗粒蛋白前体。在本研究中，我们研究了GP 88在ER+乳腺癌细胞中获得对来曲唑耐药的作用。我们使用两种芳香化酶过表达的人乳腺癌细胞系MCF-7-CA细胞和AC 1细胞及其来曲唑耐药对应物作为研究模型。检测了刺激或抑制GP 88表达对增殖、锚定非依赖性生长、存活和来曲唑反应性的影响。GP 88诱导细胞增殖并以时间和剂量依赖性方式赋予来曲唑抗性。相反，与来曲唑敏感细胞相比，天然来曲唑耐药乳腺癌细胞显示GP 88表达增加10倍。GP 88过表达或外源性添加阻断来曲唑对增殖的抑制作用，并刺激存活和软琼脂集落形成。在来曲唑耐药细胞中，通过siRNA沉默GP 88抑制细胞增殖并恢复其对来曲唑的敏感性。我们的研究结果提供了关于替代生长和存活因子在ER+乳腺癌中获得芳香化酶抑制剂抗性的作用的信息。
Aromatase inhibitors (AI) that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+) breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88), also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined. GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole. Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.
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影响因子：
--
作者：
Oh, AS;Lorant, LA;El-Ashry, D
通讯作者：
El-Ashry, D
DOI：
10.1016/j.jsbmb.2004.12.006
发表时间：
2005-02-01
影响因子：
4.1
作者：
Nicholson, RI;Hutcheson, IR;Gee, JMW
通讯作者：
Gee, JMW
影响因子：
3.9
作者：
Chen, S;Zhou, D;Yang, C
通讯作者：
Yang, C
影响因子：
15.9
作者：
Elkabets, Moshe;Gifford, Ann M.;McAllister, Sandra S.
通讯作者：
McAllister, Sandra S.
影响因子：
4.8
作者：
McClelland, RA;Barrow, D;Nicholson, RI
通讯作者：
Nicholson, RI