维甲酸受体β通过促进人乳腺癌细胞凋亡来介导维甲酸的生长抑制作用。
Retinoic acid receptor beta mediates the growth-inhibitory effect of retinoic acid by promoting apoptosis in human breast cancer cells.
作者信息
Liu Y, Lee M O, Wang H G, Li Y, Hashimoto Y, Klaus M, Reed J C, Zhang X
机构信息
La Jolla Cancer Research Foundation, Cancer Research Center, La Jolla, California 92037, USA.
出版信息
Mol Cell Biol. 1996 Mar;16(3):1138-49. doi: 10.1128/MCB.16.3.1138.
Retinoids are known to inhibit the growth of hormone-dependent but not that of hormone-independent breast cancer cells. We investigated the involvement of retinoic acid (RA) receptors (RARs) in the differential growth-inhibitory effects of retinoids and the underlying mechanism. Our data demonstrate that induction of RAR beta by RA correlates with the growth-inhibitory effect of retinoids. The hormone-independent cells acquired RA sensitivity when the RAR beta expression vector was introduced and expressed in the cells. In addition, RA sensitivity of hormone-dependent cells was inhibited by a RAR beta-selective antagonist and the expression of RAR beta antisense RNA. Introduction of RAR alpha also restored RA sensitivity in hormone-independent cells, but this restoration was accomplished by the induction of endogenous RAR beta expression. Furthermore, we show that induction of apoptosis contributes to the growth-inhibitory effect of RAR beta. Thus, RAR beta can mediate retinoid action in breast cancer cells by promoting apoptosis. Loss of RAR beta, therefore, may contribute to the tumorigenicity of human mammary epithelial cells.
已知维甲酸可抑制激素依赖性乳腺癌细胞的生长，但对激素非依赖性乳腺癌细胞无效。我们研究了维甲酸（RA）受体（RARs）在维甲酸的差异生长抑制作用及其潜在机制中的作用。我们的数据表明，RA诱导RARβ与维甲酸的生长抑制作用相关。当将RARβ表达载体导入并在激素非依赖性细胞中表达时，这些细胞获得了对RA的敏感性。此外，RARβ选择性拮抗剂和RARβ反义RNA的表达可抑制激素依赖性细胞对RA的敏感性。导入RARα也可恢复激素非依赖性细胞对RA的敏感性，但这种恢复是通过诱导内源性RARβ表达实现的。此外，我们发现诱导细胞凋亡有助于RARβ的生长抑制作用。因此，RARβ可通过促进细胞凋亡介导维甲酸在乳腺癌细胞中的作用。因此，RARβ的缺失可能导致人乳腺上皮细胞的致瘤性。
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