Expression of midkine in the early stage of carcinogenesis in human colorectal cancer

Expression of midkine in the early stage of carcinogenesis in human colorectal cancer
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DOI:
10.1038/sj.bjc.6690030
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发表时间:
1999-01-01
影响因子:
8.8
通讯作者:
Kadomatsu, K
Kadomatsu, K
中科院分区:
医学1区
文献类型:
--
作者:
Ye, C;Qi, M;Kadomatsu, K

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研究表明,肝素结合生长因子中期因子(MK)在多种恶性肿瘤中频繁过表达,在肿瘤发生发展中起重要作用。为探讨MK是否参与癌变的早期阶段,我们用Northern印迹法检测了20例中重度不典型增生腺瘤、28例癌组织和28例相应正常组织中MK基因的表达情况。MK在腺瘤中的表达水平显著高于正常组织(P<0.001,非配对学生t检验)。在癌组织和相应的正常组织之间也观察到差异(P<0.4,配对学生t检验)。MK免疫染色在中、重度不典型增生的腺瘤和癌组织中呈阳性表达,而在轻度不典型增生和正常组织中均不表达。这些发现与Western blotting的结果一致。在3例伴有中、重度不典型增生的腺瘤和癌中,观察到肿瘤病变中MK的表达升高。这是关于MK表达升高与人类早期癌变相关的第一份报告。
It has been suggested that a heparin-binding growth factor, midkine (MK), plays an important role in carcinogenesis because of its frequent overexpression in various malignant tumours. To clarify whether or not MK contributes to the early stage of carcinogenesis, we examined the status of MK mRNA in 20 adenomas with moderate- and severe-grade dysplasia, 28 carcinomas and 28 corresponding normal tissues, by means of Northern blotting. The MK expression level was significantly more elevated in adenomas than in normal tissues (P< 0.001, unpaired Student's t-test). A difference was also observed between carcinomas and the corresponding normal tissues (P< 0.4, paired Student's t-test). Moreover, MK immunostaining was positive in the adenomas with moderate- and severe-grade dysplasia and in the carcinomas, but not in mild-grade dysplasia or in normal tissues. These findings were in line with those on Western blotting. In three patients with both adenomas with moderate- or severe-grade dysplasia and carcinomas, elevated MK expression was observed in the neoplastic lesions. This is the first report of the association of elevated MK expression with the early stage of carcinogenesis in humans.