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HsMCM2/BM28:
A Novel Proliferation Marker for Human Tumors and Normal Tissues |
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Ivan T. Todorov,
Bruce A. Werness, Hui-Qun Wang, Laxmi N. Buddharaju, Pechka D. Todorova,
Harry K. Slocum, John S. J. Brooks, and Joel A. Huberman |
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Departments
of Molecular and Cellular Biology (ITT, LNB, PDT, JAH) and Pathology (BAW,
H-QW, HKS, JSJB), Roswell Park Cancer Institute, Buffalo, New York; and
Desmos, Inc. (ITT), San Diego, California |
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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. |
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