维甲酸受体-β在口腔癌前病变中的抑制作用及其被异维甲酸上调的现象。

Suppression of retinoic acid receptor-beta in premalignant oral lesions and its up-regulation by isotretinoin.

作者信息

Lotan R, Xu X C, Lippman S M, Ro J Y, Lee J S, Lee J J, Hong W K

机构信息

Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

出版信息

N Engl J Med. 1995 May 25;332(21):1405-10. doi: 10.1056/NEJM199505253322103.

DOI:10.1056/NEJM199505253322103

PMID:7723796

Abstract

BACKGROUND

Retinoids are effective in the treatment and prevention of certain human cancers. Most of their actions are thought to result from changes in gene expression mediated by nuclear retinoic acid receptors and retinoid X receptors. We conducted a study to determine whether the expression of these receptors was altered in premalignant oral lesions and, if so, whether their expression could be restored by treatment with isotretinoin.

METHODS

We performed in situ hybridization of retinoic acid receptors and retinoid X receptors using antisense riboprobes in specimens of oral mucosa from 7 normal subjects and specimens of premalignant oral lesions from 52 patients before treatment with isotretinoin and from 39 of the 52 patients after three months of treatment.

RESULTS

All the normal specimens expressed retinoic acid receptor-beta messenger RNA (mRNA). In contrast, retinoic acid receptor-beta mRNA was detected in only 21 of the 52 premalignant oral lesions (P = 0.003). Thirty-five of the 39 specimens available for evaluation after treatment expressed retinoic acid receptor-beta mRNA (P < 0.001). All normal and premalignant specimens expressed similar levels of mRNA for retinoic acid receptor-alpha and retinoic acid receptor-gamma and the three types of retinoic X receptors, alpha, beta, and gamma. The levels of retinoic acid receptor-beta mRNA increased in the specimens from 18 of the 22 patients who had responses to isotretinoin and in 8 of the 17 specimens from the patients without responses (P = 0.04).

CONCLUSIONS

The expression of retinoic acid receptor-beta mRNA is selectively lost in premalignant oral lesions and can be restored by treatment with isotretinoin. Restoration of the expression of retinoic acid receptor-beta mRNA is associated with a clinical response. Retinoic acid receptor-beta may have a role in mediating the response to retinoids and may be a useful intermediate biologic marker in trials of these agents for the prevention of oral carcinogenesis.

摘要

背景

维甲酸在某些人类癌症的治疗和预防中有效。其大多数作用被认为是由核视黄酸受体和视黄酸X受体介导的基因表达变化所致。我们进行了一项研究，以确定这些受体的表达在口腔癌前病变中是否改变，以及如果改变，其表达是否能用异维甲酸治疗恢复。

方法

我们使用反义核糖探针，对7名正常受试者的口腔黏膜标本以及52例患者在接受异维甲酸治疗前的口腔癌前病变标本和52例患者中39例治疗三个月后的标本进行视黄酸受体和视黄酸X受体的原位杂交。

结果

所有正常标本均表达视黄酸受体-β信使核糖核酸（mRNA）。相比之下，52例口腔癌前病变中仅21例检测到视黄酸受体-β mRNA（P = 0.003）。治疗后可供评估的39例标本中有35例表达视黄酸受体-β mRNA（P < 0.001）。所有正常和癌前标本对视黄酸受体-α、视黄酸受体-γ以及三种类型的视黄酸X受体α、β和γ表达相似水平的mRNA。在对异维甲酸有反应的22例患者中的18例患者的标本以及无反应患者的17例标本中的8例标本中，视黄酸受体-β mRNA水平升高（P = 0.04）。