探讨维甲酸在预防和治疗肿瘤中的作用机制，分离受维甲酸调控的靶基因。 方法： 采用AP PCR、测序、Northern杂交及序列同源分析等方法。 结果： 首次发现ATRA可上调线粒体基因ATP酶第六亚单位表达， 这种表达上调开始于ATRA诱导早期并持续整个诱导过程(7 d）。Northern杂交结果证实了ATRA对线粒体基因ATP酶第六亚单位的上调作用。对线粒体基因组的转录调控区D loop序列进行了初步分析发现，该转录调控区两处存在着与维甲酸受体反应元件核心序列高度一致的外翻重复序列（everted repeated sequences），其间隔分别为12 bp和13 bp。 结论： 维甲酸受体与线粒体基因组维甲酸反应元件相互作用可能是其调控线粒体基因的表达。 维甲酸除调控核基因外, 亦可对线粒体基因进行直接调控。

To explore the mechanism of prevention and therapy by retinoic acid in cancer and isolate ATRA-target gene and explore the mechanism of expression regulation of mitochondrial gene. Methods： AP-PCR, hybridization, sequencing etc., were used. Results ： ATRA up-regulated the expression of mitochondrion gene ATPase subunit 6, the change lasted in whole period of ATRA treatment (from first day to seventh day). The up-regulation was confirmed by Northen blot analysis. Two possible retinoic acid responsive elements (RAREs) were located in the regulation region of mitochondrion genome. Conclusion： The mitochondrion gene expression by ATRA might be regulated through the interaction of retinoic acid receptor (RAR) with RARE in mitochondrion genome

R730.3

* 本课题为国家攀登计划项目(G1998051205)和“863”项目(Z19-01-01-02)资助