Nuclear retinoid acid receptor beta in bronchial epithelium of smokers before and during chemoprevention.
Nuclear retinoid acid receptor beta in bronchial epithelium of smokers before and during chemoprevention.
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化学预防之前和期间吸烟者支气管上皮中的核视黄酸受体β。
DOI：
10.1093/jnci/91.15.1317
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Lotan,R
中科院分区：
文献类型：
--
作者：
Xu,XC;Lee,JS;Lee,JJ;Morice,RC;Liu,X;Lippman,SM;Hong,WK;Lotan,R
背景：维甲酸可以逆转肿瘤病变，预防呼吸道的第二原发癌。这些作用被认为是由核维甲酸受体(RARs)和维甲酸X受体(RXRs)介导的，每个受体组包括三个亚型(α，β和γ)。此前，我们发现RARβ在肺癌中的表达受到抑制。在这项研究中，我们研究了化学预防性干预是否调节了RARβ的表达。方法：采用原位杂交技术，分析重度吸烟者、13-顺式维甲酸(13-cis-RA)或安慰剂治疗6个月后支气管活检标本中RARmRNA的β表达。由于我们之前在90%的非吸烟者的支气管标本中检测到RARβ的表达，我们认为在本研究基线的六个活检标本中至少有一个的RARβ表达缺失是异常的。结果：13-顺-RA组35例患者中有30例(85.7%)RARβ基因表达异常，而安慰剂组33例患者中有24例(72.7%)表达异常。经13-顺式维甲酸治疗6个月后，所有6例活检标本中RARβ阳性的人数从5例增加到13例(2.6倍)，RARβ异常表达的个体百分比下降到62.9%(22/35)，与基线表达相比有统计学意义(双侧P=0.01)。在安慰剂组中，RARβ的表达在基线和6个月之间没有统计学意义上的差异。RARβ的表达与当前吸烟状态或鳞状化生逆转无关。结论：RARβ是13-顺式-RA应答的独立标志物，可作为上呼吸道癌化学预防试验的中间生物标志物。
BACKGROUND: Retinoids can reverse neoplastic lesions and prevent second primary tumors in the aerodigestive tract. These effects are thought to be mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each receptor group including three subtypes (α, β , and γ). Previously, we found that RARβ expression was suppressed in lung cancer. In this study, we investigated whether expression of RARβ is modulated by chemopreventive intervention. METHODS: Usingin situhybridization, we analyzed RARβ messenger RNA (mRNA) expression in bronchial biopsy specimens from heavy smokers, at baseline and after 6 months of treatment with 13-cis-retinoic acid (13-cis-RA) or placebo. Since we had previously detected RARβ expression in 90% of bronchial specimens from nonsmokers, we considered loss of RARβ mRNA expression in at least one of six biopsy specimens at baseline in this study to be aberrant. RESULTS: RARβ mRNA expression was aberrant in 30 (85.7%) of 35 subjects in the 13-cis-RA group and in 24 (72.7%) of 33 subjects in the placebo group. After 6 months of 13-cis-RA treatment, the number of subjects who were RARβ positive in all six biopsy specimens increased from five of 35 to 13 of 35 (2.6-fold), so that the percentage of individuals with aberrant RARβ expression decreased to 62.9% (22 of 35), which represents a statistically significant difference from baseline expression (two-sidedP= .01). In the placebo group, no statistically significant difference in RARβ expression was observed between baseline and 6 months. RARβ expression was not related to current smoking status or reversal of squamous metaplasia. CONCLUSIONS: These results indicate that RARβ is an independent marker of response to 13-cis-RA and may serve as an intermediate biomarker in chemoprevention trials of upper aerodigestive tract cancers.
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人类肺癌中视黄酸受体β异常的发生率较高。
影响因子：
8
作者：
Gebert,JF;Moghal,N;Frangioni,JV;Sugarbaker,DJ;Neel,BG
通讯作者：
Neel,BG
影响因子：
11.2
作者：
X. C. Xu;Jae Y. Ro;J. S. Lee;Dong M. Shin;W. Hong;R. Lotan
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影响因子：
3.7
作者：
Clara Nervi;T. Vollberg;M. D. George;Arthur Zelent;P. Chambon;A. M. Jetten
通讯作者：
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不典型化生和支气管癌的发病率。
影响因子：
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作者：
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通讯作者：
G. Samsa
影响因子：
4.8
作者：
Berard, J;Laboune, F;Bradley, WEC
通讯作者：
Bradley, WEC