A retinoid X receptor (RXR)-selective retinoid reveals that RXR-alpha is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands.
A retinoid X receptor (RXR)-selective retinoid reveals that RXR-alpha is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands.
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DOI：
10.1186/bcr913
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Chandraratna RA
中科院分区：
文献类型：
--
作者：
Crowe DL;Chandraratna RA
某些脂质已被证明是核激素受体超家族的一个亚群的配体，称为过氧化体增殖物激活受体(PPAR)。这些转录因子的配体已经用于实验性的癌症治疗。PPAR与维甲酸X受体(RXRs)异源二聚并与DNA结合，RXRs与核受体超家族的其他成员具有同源性。维甲酸已被发现对许多类型的癌症有效。然而，许多乳腺癌对这些药物的化疗效果产生了抗药性。最近，RXR选择性配体被发现在体外抑制全反式维甲酸耐药的乳腺癌细胞的增殖，并在动物模型中导致疾病的消退。关于使用PPAR和RXR配体进行联合治疗预防或治疗乳腺癌的疗效，发表的研究很少。我们在体外测定了选择性PPAR和RXR配体对已建立的人乳腺癌细胞系的影响。PPAR-α和PPAR-γ配体分别诱导人乳腺癌细胞株的凋亡和抗增殖反应，这与基因表达的特异性变化有关。这些反应被RXR选择性配体AGN194204增强。有趣的是，RXR-α过表达的维甲酸耐药乳腺癌细胞株对RXR选择性化合物的作用更敏感。RXR选择性维甲酸可以增强乳腺癌细胞对PPAR配体的抗增殖和凋亡反应。
Certain lipids have been shown to be ligands for a subgroup of the nuclear hormone receptor superfamily known as the peroxisome proliferator-activated receptors (PPARs). Ligands for these transcription factors have been used in experimental cancer therapies. PPARs heterodimerize and bind DNA with retinoid X receptors (RXRs), which have homology to other members of the nuclear receptor superfamily. Retinoids have been found to be effective in treating many types of cancer. However, many breast cancers become resistant to the chemotherapeutic effects of these drugs. Recently, RXR-selective ligands were discovered that inhibited proliferation of all-trans retinoic acid resistant breast cancer cells in vitro and caused regression of the disease in animal models. There are few published studies on the efficacy of combined therapy using PPAR and RXR ligands for breast cancer prevention or treatment. We determined the effects of selective PPAR and RXR ligands on established human breast cancer cell lines in vitro. PPAR-α and PPAR-γ ligands induced apoptotic and antiproliferative responses in human breast cancer cell lines, respectively, which were associated with specific changes in gene expression. These responses were potentiated by the RXR-selective ligand AGN194204. Interestingly, RXR-α-overexpressing retinoic acid resistant breast cancer cell lines were more sensitive to the effects of the RXR-selective compound. RXR-selective retinoids can potentiate the antiproliferative and apoptotic responses of breast cancer cell lines to PPAR ligands.
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DOI：
10.1111/j.1349-7006.1999.tb00668.x
发表时间：
1999-01
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Kitamura S;Miyazaki Y;Shinomura Y;Kondo S;Kanayama S;Matsuzawa Y
通讯作者：
Matsuzawa Y
影响因子：
16
作者：
Mueller, E;Sarraf, P;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
64.8
作者：
Kersten, S;Desvergne, B;Wahli, W
通讯作者：
Wahli, W
影响因子：
64.8
作者：
KLIEWER, SA;UMESONO, K;EVANS, RM
通讯作者：
EVANS, RM
影响因子：
64.5
作者：
KLIEWER, SA;LENHARD, JM;LEHMANN, JM
通讯作者：
LEHMANN, JM