Overexpression of the homeobox gene HOXC8 in human prostate cancer correlates with loss of tumor differentiation
Overexpression of the homeobox gene HOXC8 in human prostate cancer correlates with loss of tumor differentiation
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DOI：
10.1002/pros.10045
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发表时间：
2002-02-15
期刊：
影响因子：
2.8
通讯作者：
Castronovo, V
中科院分区：
文献类型：
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作者：
Waltregny, D;Alami, Y;Castronovo, V
背景资料。含有同源异型盒(Homeobox，HOX)的蛋白质被认为是控制发育和分化相关基因协调表达的调节因子。最近的数据还表明，HOX基因可能参与了恶性转化和/或进展。与正常角质形成细胞相比，HOXC8在人宫颈癌细胞中的表达被选择性地打开，提示HOXC8可能参与了导致宫颈角质形成细胞转化的过程[Alami等：Biochem BiPhys Commun 257：738-745,1999]。方法采用RT-PCR和原位杂交实验研究HOXC8转录本在人前列腺癌细胞系和组织中的表达和细胞类型定位。用HOXC8反义地高辛标记的探针进行原位杂交，检测27例前列腺癌组织中HOXC8基因的表达。结果：在所检测的三种人前列腺癌细胞系中，DU-145和PC3细胞表达HOXC8基因，而LNCaP细胞不表达HOXC8基因。原位杂交结果表明，HOXC8基因主要在恶性上皮细胞中表达。此外，在高Gleason评分(7-9分，n=12；标记强度2+-3+)的前列腺癌中，上皮细胞的染色强度显著高于低和中等Gleason评分的肿瘤(评分3-6，n=15；标记强度0和1+)(方差分析检验，P<；0.0001)。结论：我们的数据表明，HOXC8在前列腺癌中的过度表达与肿瘤分化的丧失有关，提示HOXC8可能在前列腺癌侵袭和转移表型的获得中起作用。(C)2002年Wiley-Liss，Inc.
BACKGROUND. Homeobox (HOX)-containing proteins have been identified as regulators controlling the coordinated expression of genes involved in development and differentiation. Recent data also suggest a possible involvement of HOX genes in malignant transformation and/or progression. We have previously shown that HOXC8 expression was selectively turned on in human cervix cancer cells compared with normal keratinocytes, suggesting that HOXC8 may be involved in the process leading to the transformation of cervix keratinocytes [Alami et al.: Biochem Biophys Res Commun 257:738-745,1999].METHODS. RT-PCR and in situ hybridization experiments were performed to investigate the expression and cell type localization of HOXC8 transcripts in human prostate cancer cell lines and tissues. In situ hybridization was performed with the use of an HOXC8 anti-sense digoxigenin-labeled probe to investigate HOXC8 mRNA expression in 27 prostate cancer tissue specimens.RESULTS. Out of the three human prostate cancer cell lines tested, DU-145 and PC3 but not LNCaP cells expressed detectable amount of HOXC8 transcripts. Results from in situ hybridization experiments demonstrated that HOXC8 gene was expressed mainly in malignant epithelial cells. Furthermore, the staining intensity in epithelial cells was significantly increased in high Gleason score carcinomas (scores 7-9, n = 12; labeling intensity 2 + to 3 +) compared with the one observed in low and intermediate Gleason score tumors (scores 3-6, n = 15; labeling intensity 0 and 1 +) (ANOVA test, P < 0.0001).CONCLUSIONS. Our data showing that HOXC8 overexpression is associated with the loss of tumor differentiation in human prostate cancer suggests that HOXC8 may play a role in the acquisition of the invasive and metastatic phenotype of this malignancy. (C) 2002 Wiley-Liss, Inc.