Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa
Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa
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DOI：
10.3748/wjg.v11.i17.2616
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发表时间：
2005-05-07
影响因子：
4.3
通讯作者：
Pastorek, Jaromir
中科院分区：
文献类型：
--
作者：
Kivela, Antti J.;Parkkila, Seppo;Pastorek, Jaromir
目的：为探讨CA IX/CA XII与pVHL在正常大肠粘膜和大肠癌组织中表达的关系，采用免疫组化方法对17例大肠癌患者的42例大肠癌组织标本进行CA IX、CA XII和pVHL的分布和半定量分析。采用RT-PCR扩增14例新鲜冰冻肿瘤的VHL mRNA并进行测序。通过半定量RT-PCR分析CA 9和CA 12 mRNA水平，并与作为缺氧指标的VEGF进行比较，以解除pVHL对照的偶联。结果：肿瘤组织与CA IX染色信号的临界增加和CA XII免疫反应性的轻微但显着的降低相关，而没有发现与pVHL相关。RT-PCR扩增的VHL mRNA的序列分析显示没有缺失/突变，这表明它们是VHL感受态的。我们没有观察到pVHL和CA IX/CA XII蛋白以及VEGF和CA 9 mRNA之间的任何相关性，但VEGF和CA 12 mRNA水平的肿瘤相关变化显示出显著的负相关性。我们的研究结果表明，CA 9和CA 12受不同的肿瘤内因素调节，CA IX/CA 12水平之间缺乏明显的关系。CA XII和pVHL不能完全归因于pVHL的负调节功能通过诱导的VEGF转录所表示的肿瘤缺氧而解偶联。结直肠肿瘤中功能性pVHL和CA IX/CA XII之间的相互作用似乎相当复杂，仅在表达水平上并不明显。(C)2005年WJG出版社和Elsevier Inc. All rights reserved.
AIM: To analyze possible relationships between CA IX/CA XII and pVHL expression in normal and neoplastic colorectal mucosa.METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA IX, CA XII and pVHL. VHL mRNAs from 14 fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and CA12 mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGF as an indicator of hypoxia that uncouples the pVHL control.RESULTS: Tumor tissues were associated with a borderline increase of CA IX staining signal and slight but significant decrease of CA XII immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL and CA IX/CA XII proteins as well as between VEGF and CA9 mRNAs, but the tumor-associated changes in mRNA levels of VEGF and CA12 showed a significant inverse relationship.CONCLUSION: Our results indicate that CA9 and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA IX/CA XII and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA IX/CA XII in colorectal tumors seems rather complex and is not evident merely at the expression levels. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.