Aryl hydrocarbon receptor ligands inhibit igf-ii and adipokine stimulated breast cancer cell proliferation.
Aryl hydrocarbon receptor ligands inhibit igf-ii and adipokine stimulated breast cancer cell proliferation.
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DOI：
10.1155/2013/104850
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发表时间：
2013
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影响因子：
--
通讯作者：
Santanam N
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文献类型：
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作者：
Salisbury TB;Morris GZ;Tomblin JK;Chaudhry AR;Cook CR;Santanam N
肥胖增加了人类患癌症的风险和癌症复发的风险。脂肪细胞分泌被称为脂肪因子的旁分泌因子，刺激癌细胞信号传导，诱导增殖。芳烃受体（aryl hydrocarbon receptor， AHR）是一种配体激活的转录因子，在肿瘤发生过程中发挥重要作用，受外源性亲脂化学物质的调控，已被探索为癌症治疗的靶点。外源性AHR配体是否调节脂肪因子刺激乳腺癌细胞增殖尚未研究。我们提供的证据表明，脂肪细胞分泌胰岛素样生长因子2 （IGF-2）的水平可以刺激人类雌激素受体（ER）阳性乳腺癌细胞的增殖。利用高度特异性AHR配体和AHR短干扰RNA (AHR- sirna)，我们发现特异性配体激活的AHR抑制脂肪细胞分泌组和igf -2刺激的乳腺癌细胞增殖。我们还报道了一种高度特异性的AHR激动剂显著（P < 0.05）抑制乳腺癌细胞中E2F1、CCND1（称为Cyclin D1）、MYB、SRC、JAK2和JUND的表达。总的来说，这些数据表明，针对AHR的药物可能对治疗人类肥胖的癌症有用。
Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly (P < 0.05) inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity.