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人类结肠腺瘤性息肉中结肠癌特异性核基质蛋白改变

Colon cancer specific nuclear matrix protein alterations in human colonic adenomatous polyps.

作者信息

Brünagel Gisela, Schoen Robert E, Getzenberg Robert H

机构信息

Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA.

出版信息

J Cell Biochem. 2004 Feb 1;91(2):365-74. doi: 10.1002/jcb.10695.

Abstract

Most colon cancers arise within preexisting adenomatous polyps or adenomas. The slow evolution from the non-invasive premalignant lesion, the adenomatous polyp, to invasive cancer supports a strategy of early detection. Recently, we identified unique nuclear matrix proteins (NMPs) specific for colon cancer (CC2, CC3, CC4, CC5). Most of the NMPs identified are common to all cell types, but several identified NMPs are tissue and cell line specific. The objective of this study is to describe and characterize the NMP profile of premalignant adenomatous colon polyps. Specifically when in the adenoma-carcinoma sequence four specific colon cancer NMPs, previously described, appear. Using two-dimensional (2-D) gel analysis 20 colon polyps (one juvenile polyp, six tubular adenoma (TA), seven tubulovillous adenoma (TVA), six TVA with focal high-grade dysplasia (HGD), were analyzed for the presence of four (CC2, CC3, CC4, CC5) specific NMPs. CC2 was not seen in any of the premalignant polyps. CC5 was present in only two premalignant TVA with HGD and in one TA. CC3 and CC4 were present in most adenomas. None of the NMPs were seen in the juvenile polyp, which is not considered to be a precursor of colon cancer. CC2 and CC5 are NMPs expressed at the junction of an advanced adenoma and invasive colorectal cancer. CC3 and CC4 are expressed earlier in the evolution of adenomatous polyps. Development of an assay to these proteins may serve as a new method for early detection of colorectal cancer.

摘要

大多数结肠癌起源于先前存在的腺瘤性息肉或腺瘤。从非侵袭性癌前病变腺瘤性息肉缓慢演变为侵袭性癌症,这支持了早期检测的策略。最近,我们鉴定出了结肠癌特有的独特核基质蛋白(NMPs,即CC2、CC3、CC4、CC5)。所鉴定出的大多数NMPs在所有细胞类型中都很常见,但有几种鉴定出的NMPs是组织和细胞系特异性的。本研究的目的是描述和表征癌前腺瘤性结肠息肉的NMPs谱。具体而言,在腺瘤-癌序列中,先前描述的四种特定结肠癌NMPs何时出现。使用二维(2-D)凝胶分析,对20个结肠息肉(1个幼年息肉、6个管状腺瘤(TA)、7个绒毛管状腺瘤(TVA)、6个伴有局灶性高级别异型增生(HGD)的TVA)进行分析,以检测四种(CC2、CC3、CC4、CC5)特定NMPs的存在情况。在任何癌前息肉中均未发现CC2。CC5仅在两个伴有HGD的癌前TVA和一个TA中存在。CC3和CC4在大多数腺瘤中存在。在幼年息肉中未发现任何NMPs,幼年息肉不被认为是结肠癌的前体。CC2和CC5是在晚期腺瘤与侵袭性结直肠癌交界处表达的NMPs。CC3和CC4在腺瘤性息肉演变过程中更早表达。开发针对这些蛋白的检测方法可能成为早期检测结直肠癌的新方法。

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