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9-顺式视黄酸对人乳腺癌细胞生长及视黄酸X受体表达的影响。

Effect of 9-cis-retinoic acid on growth and RXR expression in human breast cancer cells.

作者信息

Zhao Z, Zhang Z P, Soprano D R, Soprano K J

机构信息

Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.

出版信息

Exp Cell Res. 1995 Aug;219(2):555-61. doi: 10.1006/excr.1995.1264.

Abstract

A number of studies have demonstrated the ability of retinoic acid (RA) to inhibit the growth of estrogen receptor-positive (ER+) human breast cancer cell lines. The precise mechanism of growth inhibition is not known. However, the biological effects of RA in other model systems have been shown to be mediated via the nuclear retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). While several laboratories have examined the expression of RARs in various breast cancer cell lines, no information is available concerning the role of the RXRs and 9-cis-RA, the natural ligand of RXRs, in the response of breast cancer cells to RA. Using a representative panel of breast cancer cell lines, we determined the effect of 9-cis-RA on growth and cell cycle stage distribution, analyzed steady-state mRNA levels of RXR-alpha, -beta, and -gamma, and determined the effect of all-trans-RA and 9-cis-RA on RXR expression. Our results show that: (1) the growth of ER+/RA-sensitive breast cancer cells is inhibited by treatment with 9-cis-RA by blocking entry into S phase; (2) both ER+/RA-sensitive and ER-/RA-resistant breast cancer cell lines express RXR-alpha and RXR-beta mRNAs but not RXR-gamma; however, levels of these transcripts did not correlate with the RA response; and (3) levels of RXR-alpha and RXR-beta mRNA were not significantly altered following treatment with either all-trans-RA or 9-cis-RA. These results suggest that the mechanism responsible for the retinoid sensitivity of breast cancer cells does not involve transcriptional modulation of the RXRs by RA.

摘要

多项研究已证明视黄酸(RA)能够抑制雌激素受体阳性(ER+)人乳腺癌细胞系的生长。生长抑制的确切机制尚不清楚。然而,RA在其他模型系统中的生物学效应已被证明是通过核视黄酸受体(RARs)和类视黄醇X受体(RXRs)介导的。虽然有几个实验室检测了各种乳腺癌细胞系中RARs的表达,但关于RXRs及其天然配体9-顺式视黄酸(9-cis-RA)在乳腺癌细胞对RA反应中的作用尚无相关信息。我们使用一组具有代表性的乳腺癌细胞系,确定了9-顺式视黄酸对生长和细胞周期阶段分布的影响,分析了RXR-α、-β和-γ的稳态mRNA水平,并确定了全反式视黄酸(all-trans-RA)和9-顺式视黄酸对RXR表达的影响。我们的结果表明:(1)通过阻止进入S期,用9-顺式视黄酸处理可抑制ER+/RA敏感的乳腺癌细胞的生长;(2)ER+/RA敏感和ER-/RA耐药的乳腺癌细胞系均表达RXR-α和RXR-β的mRNA,但不表达RXR-γ;然而,这些转录本的水平与RA反应无关;(3)用全反式视黄酸或9-顺式视黄酸处理后,RXR-α和RXR-β的mRNA水平没有明显改变。这些结果表明,乳腺癌细胞类视黄醇敏感性的机制不涉及RA对RXRs的转录调节。

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