A conserved tissue-specific homeodomain-less isoform of MEIS1 is downregulated in colorectal cancer.
A conserved tissue-specific homeodomain-less isoform of MEIS1 is downregulated in colorectal cancer.
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DOI：
10.1371/journal.pone.0023665
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Buchberg AM
中科院分区：
文献类型：
--
作者：
Crist RC;Roth JJ;Waldman SA;Buchberg AM
结直肠癌是发达国家最常见的癌症之一，是环境和遗传因素共同作用的结果。在结直肠癌中观察到的许多遗传病变改变了编码同源异型域转录因子的同源异型盒基因的表达。已知MEIS 1同源框基因参与几种血液恶性肿瘤和实体瘤，最近的证据表明MEIS 1转录物的表达在结直肠癌中改变。尽管存在这种潜在的联系，但人们对该基因在肠道中的作用知之甚少。我们探测小鼠胃肠道组织样本的N-末端Meis 1抗体，揭示了两个先前描述的亚型，以及两个新的Meis 1产品的表达。一个32 kD的Meis 1产物在胃和结肠的非上皮细胞的细胞核中表达，而一个27 kD的产物在近端结肠的上皮细胞的细胞质中表达。我们的数据表明，27 kD和32 kD的Meis 1蛋白都是Meis 1d蛋白的形式，Meis 1d蛋白是一种同源结构域较少的同种型，其转录本先前在cDNA筛选中被鉴定。MEIS 1D转录本和蛋白质均在人结肠粘膜中表达。与匹配的正常粘膜相比，MEIS 1D蛋白的表达在83%（10/12）的原发性结直肠癌样品中下调，表明MEIS 1D是结直肠肿瘤发生的生物标志物。MEIS 1D在结肠肿瘤中的表达降低也表明这种保守的同源结构域较少的同种型可能在人类结直肠癌中充当肿瘤抑制因子。
Colorectal cancer is one of the most common cancers in developed nations and is the result of both environmental and genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encode homeodomain transcription factors. The MEIS1 homeobox gene is known to be involved in several hematological malignancies and solid tumors and recent evidence suggests that expression of the MEIS1 transcript is altered in colorectal cancer. Despite this potential connection, little is known about the role of the gene in the intestines. We probed murine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing expression of two previously described isoforms, as well as two novel Meis1 products. A 32 kD Meis1 product was expressed in the nuclei of non-epithelial cells in the stomach and colon, while a 27 kD product was expressed in the cytoplasm of epithelial cells in the proximal colon. Our data suggest that the 27 kD and 32 kD Meis1 proteins are both forms of the Meis1d protein, a homeodomain-less isoform whose transcript was previously identified in cDNA screens. Both the MEIS1D transcript and protein were expressed in human colon mucosa. Expression of the MEIS1D protein was downregulated in 83% (10/12) of primary colorectal cancer samples compared to matched normal mucosa, indicating that MEIS1D is a biomarker of colorectal tumorigenesis. The decreased expression of MEIS1D in colon tumors also suggests that this conserved homeodomain-less isoform may act as a tumor suppressor in human colorectal cancer.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
11.6
作者：
Magnani, Enrico;Hake, Sarah
通讯作者：
Hake, Sarah
影响因子：
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作者：
Geerts, D;Schilderink, N;Versteeg, R
通讯作者：
Versteeg, R
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50.3
作者：
Petrova, Tatiana V.;Nykanen, Antti;Alitalo, Kari
通讯作者：
Alitalo, Kari
影响因子：
8.4
作者：
Crijns, A. P. G.;de Graeff, P.;de Vries, E. G. E.
通讯作者：
de Vries, E. G. E.