许 旭, 孙敬岩, 顾 林, 刘 红, 付 丽. 从表观遗传学角度探讨RAR-β2 基因在乳腺癌发生中的作用*[J]. 中国肿瘤临床, 2010, 37(23): 1326-1329. DOI: 10.3969/j.issn.1000-8179.2010.23.002
引用本文: 许 旭, 孙敬岩, 顾 林, 刘 红, 付 丽. 从表观遗传学角度探讨RAR-β2 基因在乳腺癌发生中的作用*[J]. 中国肿瘤临床, 2010, 37(23): 1326-1329. DOI: 10.3969/j.issn.1000-8179.2010.23.002
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XU Xu, SUN Jingyan, GU Lin, LIU Hong, FU Li. Epigenetic Regulation of Retinoic Acid Receptorβ2 Gene in the Carcinogenesis of Breast Cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(23): 1326-1329. DOI: 10.3969/j.issn.1000-8179.2010.23.002
Citation: XU Xu, SUN Jingyan, GU Lin, LIU Hong, FU Li. Epigenetic Regulation of Retinoic Acid Receptorβ2 Gene in the Carcinogenesis of Breast Cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(23): 1326-1329. DOI: 10.3969/j.issn.1000-8179.2010.23.002
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从表观遗传学角度探讨RAR-β2 基因在乳腺癌发生中的作用*

Epigenetic Regulation of Retinoic Acid Receptorβ2 Gene in the Carcinogenesis of Breast Cancer

    摘要
  • 摘要: 目的：探讨视黄酸受体β 2（RAR-β 2）基因在乳腺癌、乳腺癌前病变组织中的表达改变，分析其表达情况与基因启动子甲基化状态的关系。方法：采用半定量RT-PCR 和甲基化特异PCR（MSP）方法检测120 例乳腺肿瘤组织中RAR-β 2 基因mRNA 表达情况及其启动子甲基化状态。去甲基化药物5- 氮-2'- 脱氧胞苷（5-aza-2'-deoxycytidine，5-aza-dC）处理乳腺癌细胞系MCF-7和T-47D，分别检测RAR-β 2 mRNA 表达改变和甲基化状况。结果：在mRNA 水平上，RAR-β 2 基因在乳腺癌及癌前病变组织中阳性表达率较正常乳腺及腺纤维瘤组织显著降低（P<0.05）。 MSP 结果显示，20例正常乳腺组织均未发现RAR-β 2 基因启动子的甲基化；60例乳腺癌组织中，27例（45%）检测到RAR-β 2 基因启动子的甲基化；40例乳腺癌前病变组织中，14例（35%）检测到RAR-β 2 基因启动子的甲基化；20例腺纤维瘤组织中，2 例检测到RAR-β 2 基因启动子的甲基化。乳腺癌及癌前病变组织中RAR-β 2 基因甲基化发生率均明显高于正常组织（P<0.05），乳腺癌组织甲基化发生率与癌前病变组织无显著性差异（χ2=0.99，P>0.05）。 RAR-β 2 基因表达和甲基化水平之间存在负相关（P<0.05）。 5-aza-dC 处理后，MCF-7 及T-47D 细胞系均出现RAR-β 2 基因再表达，MSP 法检测证实基因发生了去甲基化。结论：DNA甲基化是乳腺癌中 RAR-β 2 基因表达调控的一种重要机制，RAR-β 2启动子甲基化引起的基因表达下调可能与乳腺癌的发生相关。

     

    Abstract: Objective: To investigate the methylation status of retinoic acid receptor beta 2 (RAR-β 2) gene in breast cancer patients and precancerous lesions of breast cancer, and to analyze the relationship among the clinicopathologic pa-rameters, the promoter hypermethylation and mRNA expression of the RAR-β 2 gene. Methods:Semi-quantitative reverse transcription PCR (RT-PCR) was used to detect the expression of RAR-β 2 gene in 120 cases with breast tumor tissues and 20cases with non-neoplastic breast tissues. Hemi-nested methylation-specific PCR (hn-MSP) was applied to evaluate the promoter methylation status of RAR-β 2 gene. Breast cancer cell lines MCF-7 and T- 47D were treated with demethyl-ation agent5-aza-2'-deoxycytidine ( 5-aza-DC). Results: At the mRNA level , the expression of RAR-β 2 mRNA was found in 17of the 60breast cancer samples. The expression of RAR-β 2 gene was lower in breast cancer patients than in the adja -cent normal tissues or fibroadenoma samples ( P<0.05). No methylation of RAR-β 2 was detected in 20 non-neoplastic breast tissues. The promoter hypermethylation of RAR-β 2 gene was seen in 27of the 60(45%) cases with breast cancer, 14of the 40(35% ) cases with precancerous lesions of breast cancer, and only 2 of the 20cases with adenofibroma tis -sues. The posi tive rate of aberrant methylation of RAR-β 2 gene was higher in breast cancer than in the adjacent normal tis-sues ( P<0.05). There were no signi ficant di fferences in RAR-β 2 methylation level between breast cancer and precancerous lesions of breast cancer ( χ2=0.99, P>0.05). A negative correlation was found between the gene expression and methylation status of RAR-β 2 (P<0.05). No correlation was found among the methylation status, the tumor size, lymph node metasta -sis, pathological stage and histological grade, or expression of ER and PR in breast cancer (P>0.05). The expression of RAR-β 2 was restored in MCF- 7 and T- 47D after treated with 5-aza-DC. MSP detection confirmed its demethylation status in the gene. Conclusion:DNA methylation is one of mechanisms regulating the expression of RAR-β 2. The downregulation of gene expression casused by the promotor methylation of RAR-β 2 may play an important role in the carcinogenesis of breast cancer.

     

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