HsMCM2/BM28: a novel proliferation marker for human tumors and normal tissues.

HsMCM2/BM28: a novel proliferation marker for human tumors and normal tissues.
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HsMCM2/BM28:人类肿瘤和正常组织的新型增殖标志物。

DOI:
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发表时间:
1998
期刊:
Laboratory investigation; a journal of technical methods and pathology
影响因子:
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通讯作者:
J. Huberman
J. Huberman
中科院分区:
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文献类型:
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作者:
I. Todorov;B. Werness;H.;L. Buddharaju;P. D. Todorova;H. Slocum;John S. J. Brooks;J. Huberman

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HsMCM2/BM28是微小染色体维持(MCM)蛋白家族的成员,它通过帮助确保DNA在每个细胞周期只复制一次,在DNA复制中发挥关键作用。HsMCM2与DNA复制的关系向我们表明,它可能被证明是一个新的细胞增殖标记。为了验证这一可能性,我们使用免疫组织化学和免疫印迹技术研究了HsMCM2在正常人体组织和原发人类肿瘤中的表达。我们发现HsMCM2通过免疫印迹在97%的研究肿瘤中可检测到,但在相应的正常组织中仅有27%可检测到。在正常组织中,免疫印迹信号弱于肿瘤。免疫组织化学显示,正常组织中HsMCM2仅存在于增殖细胞核中。在大多数情况下,肿瘤细胞核比正常增殖细胞核产生更强的HsMCM2信号。比较研究表明,抗HsMCM2的抗体比抗增殖细胞核抗原的抗体染色的细胞核少,但通常比抗Ki-67(另一种与增殖相关的抗原)的抗体染色更多。因此,这三种蛋白质的增殖与抗原信号的相关性是不同的。这些结果表明,HsMCM2确实是一种新的细胞增殖标记。HsMCM2与肿瘤细胞核的增殖和染色强度升高(与正常增殖细胞的细胞核相比)是否会成为比增殖细胞核抗原和Ki-67更有用的诊断和预后标记物,这一事实需要进一步的研究来确定。
HsMCM2/BM28 is a member of the family of minichromosome maintenance (MCM) proteins, which play a critical role in DNA replication by helping to ensure that DNA is replicated once and only once per cell cycle. The association of HsMCM2 with DNA replication suggested to us that it might prove useful as a new marker for cell proliferation. To test this possibility, we employed immunohistochemistry and immunoblotting to study HsMCM2 expression in both normal human tissues and primary human tumors. We found that HsMCM2 was detectable by immunoblotting in 97% of the studied tumors but in only 27% of the corresponding normal tissues. In normal tissues, the immunoblot signal was weaker than in tumors. Immunohistochemistry revealed that in normal tissues HsMCM2 is present only in proliferating cell nuclei. In most cases, tumor cell nuclei produced a stronger HsMCM2 signal than normal proliferating cell nuclei. Comparative studies revealed that antibodies against HsMCM2 stained fewer nuclei than antibodies against proliferating cell nuclear antigen but usually more than antibodies against Ki-67 (another proliferation-related antigen). Thus, the correlations between proliferation and antigenic signal are different for these three proteins. These results indicate that HsMCM2 is, indeed, a novel marker for proliferating cells. Further studies are required to determine whether the fact that HsMCM2 has a different correlation with proliferation and elevated staining intensity in tumor nuclei (compared to nuclei in normal proliferating cells) will permit it to be a more useful diagnostic and prognostic marker than proliferating cell nuclear antigen and Ki-67.