Expression of retinoic acid receptor beta in human renal cell carcinomas correlates with sensitivity to the antiproliferative effects of 13-cis-retinoic acid.

Expression of retinoic acid receptor beta in human renal cell carcinomas correlates with sensitivity to the antiproliferative effects of 13-cis-retinoic acid.
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发表时间：
1996-06
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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通讯作者：
A. Hoffman;D. Engelstein;T. Bogenrieder;C. Papandreou;E. Steckelman;A. Dave;R. Motzer;E. Dmitrovsky;A. Albino;D. Nanus
A. Hoffman;D. Engelstein;T. Bogenrieder;C. Papandreou;E. Steckelman;A. Dave;R. Motzer;E. Dmitrovsky;A. Albino;D. Nanus
中科院分区：
其他
文献类型：
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作者：
A. Hoffman;D. Engelstein;T. Bogenrieder;C. Papandreou;E. Steckelman;A. Dave;R. Motzer;E. Dmitrovsky;A. Albino;D. Nanus

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视黄酸的分化和生长抑制作用是通过视黄酸核受体（RARs和RXRs）介导的，这些受体是配体激活的转录因子。最近的数据表明，RARs表达的改变和调控都以细胞环境依赖的方式与维甲酸反应有关。本研究检测了13-顺式维甲酸（cRA）对12种肾癌细胞系的抗增殖作用，并将这些发现与rar - α、- β和- γ的基础和诱导表达联系起来。Northern blot分析显示，12例对cRA有耐药性或仅被cRA最低限度抑制的肾癌中有11例不基本表达rar - β。在这些细胞中，cRA处理没有诱导rar - β表达。相比之下，12个细胞系中有1个（SK-RC-06）被cRA抑制了约90%，基本表达RARbeta。此外，通过cRA处理，SK-RC-06细胞中的rar - β mRNA表达上调。利用PCR和rar - β异构体特异性引物对扩增cDNA，发现只有SK-RC-06细胞表达rar - β异构体。rar - α转录物在所有12种细胞系中表达丰富，而在10种肾癌中的6种中检测到低水平的rar - γ转录物。rar - α和rar - γ的表达不受cRA的影响。这些数据表明，大多数肾癌细胞系对cRA具有耐药性，这表明：(a)对cRA抗增殖作用的耐药性与抑制rar - β mRNA表达相关；(b) cRA在肾癌细胞中的抗增殖作用是通过rar - β 1介导的。
The differentiation and growth suppressive effects of retinoic acid are mediated through retinoic acid nuclear receptors (RARs and RXRs), which are ligand-activated transcription factors. Recent data suggest that both altered and regulated expression of RARs are linked to retinoic acid response in a cell context-dependent manner. This study examined the antiproliferative effects of 13-cis-retinoic acid (cRA) on 12 renal cancer cell lines and correlated these findings with the basal and induced expression of RAR-alpha, -beta and -gamma. Eleven of 12 renal cancers that were either resistant to or only minimally inhibited by cRA did not basally express RAR-beta as determined by Northern blot analysis. In these cells, cRA treatment did not induce RAR-beta expression. In contrast, 1 of 12 cell lines (SK-RC-06) was >90% inhibited by cRA and basally expressed RARbeta. Furthermore, RAR-beta mRNA in SK-RC-06 cells was up-regulated by cRA treatment. Amplification of cDNA using PCR and RAR-beta isoform-specific primer pairs revealed that only SK-RC-06 cells expressed the RAR-beta1 isoform. Expression of RAR-alpha transcripts was abundant in all 12 cell lines examined, whereas low levels of RAR-gamma transcripts were detectable in 6 of 10 renal cancers. Expression of RAR-alpha and RAR-gamma was not affected by cRA. These data showing that the majority of renal cancer cell lines are resistant to cRA suggest that: (a) resistance to the antiproliferative action of cRA correlates with repressed RAR-beta mRNA expression; and (b) the antiproliferative effects of cRA in renal cancer cells are mediated through RAR-beta1.