Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues.
Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues.
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发表时间：
1994-07
期刊：
影响因子：
11.2
通讯作者：
X. C. Xu;Jae Y. Ro;J. S. Lee;Dong M. Shin;W. Hong;R. Lotan
中科院分区：
文献类型：
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作者：
X. C. Xu;Jae Y. Ro;J. S. Lee;Dong M. Shin;W. Hong;R. Lotan
类维生素A逆转上呼吸消化道癌患者的癌前病变并抑制第二原发癌的发展。据认为，这些作用是由于类维生素A恢复正常细胞生长和分化的能力。由于核维甲酸受体（RAR和RXR）是维甲酸作用的最终介质，其表达的改变可能导致癌症的发展。为了确定受体mRNA的表达是否与头颈部鳞状细胞癌（HNSCC）的发生有关，我们使用地高辛标记的RAR-α、RAR-β、RAR-γ、RXR-α和RXR-β的反义核糖核酸探针与7名正常志愿者和31名HNSCC患者的标本组织切片进行原位杂交。所有31份组织标本均含有癌，16份还含有发育不良病变，22份还含有增生病变，17份还含有邻近正常组织，6份含有所有4种类型的组织。正常志愿者的所有标本均表达5种受体。在大多数邻近的正常、增生、发育不良和恶性组织中检测到相似水平的RAR-γ和RXR-α和RXR-β mRNA。在94%的癌旁正常组织和增生组织、87%的异型增生和77%的HNSCC中检测到RAR-α mRNA。相反，在约70%的邻近正常和增生性病变中检测到RAR-β mRNA，并且其表达进一步降低至56%的不典型增生病变和35%的HNSCC。癌组织与癌旁正常组织中RAR-β水平差异有显著性（P < 0.05）。这些结果表明，RAR-β的表达减少可能与HNSCC的发展有关。
Retinoids reverse premalignant lesions and inhibit the development of second primary cancers in patients with upper aerodigestive tract cancers. It is thought that these effects result from the ability of retinoids to restore normal cell growth and differentiation. Since nuclear retinoid receptors (RARs and RXRs) are the ultimate mediators of retinoid actions, alterations in their expression could lead to cancer development. To determine whether the expression of the mRNAs of the receptors is related to the development of head and neck squamous cell carcinoma (HNSCC), we used digoxigenin-labeled antisense riboprobes of RAR-alpha, RAR-beta, RAR-gamma, RXR-alpha, and RXR-beta for in situ hybridization to histological sections of specimens from 7 normal volunteers and 31 HNSCC patients. All 31 tissue specimens contained carcinomas, 16 also contained dysplastic lesions, 22 also contained hyperplastic lesions, 17 also contained adjacent normal tissue, and 6 contained all 4 types of tissue. All specimens from normal volunteers expressed the 5 receptors. Similar levels of RAR-gamma and RXR-alpha and RXR-beta mRNAs were detected in most of the adjacent normal, hyperplastic, dysplastic, and malignant tissues. RAR-alpha mRNA was detected in 94% of adjacent normal tissues and hyperplastic tissues, in 87% of dysplasias, and in 77% of HNSCCs. In contrast, RAR-beta mRNA was detected in about 70% of adjacent normal and hyperplastic lesions, and its expression decreased further to 56% of dysplastic lesions and to 35% of HNSCCs. The difference in RAR-beta level in carcinoma and adjacent normal tissues was significant (P < 0.05). These results indicate that the decreased expression of RAR-beta may be associated with HNSCC development.