EXPRESSION OF THE HOMEOBOX GENE HOXC4 IN KERATINOCYTES OF NORMAL SKIN AND EPITHELIAL SKIN TUMORS IS CORRELATED WITH DIFFERENTIATION
EXPRESSION OF THE HOMEOBOX GENE HOXC4 IN KERATINOCYTES OF NORMAL SKIN AND EPITHELIAL SKIN TUMORS IS CORRELATED WITH DIFFERENTIATION
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DOI：
10.1111/1523-1747.ep12394888
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发表时间：
1994-09-01
影响因子：
6.5
通讯作者：
MEIJER, CJLM
中科院分区：
文献类型：
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作者：
RIEGER, E;BIJL, JJ;MEIJER, CJLM
同源异型盒（HOX）基因共享高度保守的183-bp序列。所编码的蛋白质能够与特定的DNA序列结合并作为转录因子发挥作用。HOX基因在胚胎发生过程中细胞的时间和空间分化中起着关键作用。在几个成人组织中，HOX基因的表达是一个恒定的，组织特异性的模式，而在这些组织的恶性肿瘤中的一个改变的表达模式被发现。我们研究了HOXC 4在成人正常皮肤的表达，通过逆转录聚合酶链反应和非放射性RNA原位杂交。此外，HOXC 4的表达进行了研究，在各种表皮肿瘤（日光角化病，6个标本，鲍文氏病，4个，鳞状细胞癌，9个，基底细胞癌，3）的RNA原位杂交。发现HOXC 4在正常皮肤标本的表皮基底层上和所有其他标本的相邻非病变表皮中表达。日光性角化病和Bowen病的非典型角质形成细胞以及基底细胞癌的基底细胞样细胞均为阴性。在鳞状细胞癌中，高分化角化区域显示HOXC 4表达，而低分化区域为阴性。用抗细胞角蛋白10（表皮分化的标志物）的抗体进行免疫染色。HOXC 4和细胞角蛋白10在皮损中的分布模式有很好的相关性，提示HOXC 4主要在分化的角质形成细胞中表达。缺乏分化（如在肿瘤细胞中）伴随着HOXC 4表达的下调。
Homeobox (HOX) genes share a highly conserved 183-bp sequence. The encoded proteins are capable of binding to specific DNA sequences and functioning as transcription factors. HOX genes play a critical role in the temporal and spatial differentiation of cells during embryogenesis. In several adult tissues, HOX genes are expressed in a constant, tissue-specific pattern, whereas in malignant tumors of these tissues an altered expression pattern was found. We investigated the expression of HOXC4 in adult normal skin by reverse-transcription polymerase chain reaction and non-radioactive RNA in situ hybridization. Moreover, HOXC4 expression was studied in various epidermal neoplasms (solar keratosis, six specimens; Bowen's disease, four; squamous cell carcinoma, nine; basal cell carcinoma, three) by RNA in situ hybridization. HOXC4 was found to be expressed in the suprabasal layers of the epidermis in normal skin specimens and the adjacent non-lesional epidermis of all other specimens. Atypical keratinocytes of solar keratoses and Bowen's disease as well as basaloid cells of basal cell carcinomas were negative. In squamous cell carcinoma, well differentiated areas with keratinization showed HOXC4 expression, whereas poorly differentiated areas were negative. Immunostaining with an antibody against cytokeratin 10, a marker of epidermal differentiation, was performed. A good correlation between the distribution pattern of HOXC4 and cytokeratin 10 in the lesions examined was found. These results suggest that HOXC4 is expressed mainly in differentiated keratinocytes. Lack of differentiation (as in neoplastic cells) is accompanied by downregulation of HOXC4 expression.