Proliferation markers, proliferating cell nuclear antigen, Ki67, 5-bromo-2′-deoxyuridine, and cyclin D1 in mouse olfactory epithelium

We immunohistochemically identified proliferating cells in the olfactory epithelium of mice, using an anti-proliferating cell nuclear antigen (PCNA) antibody, an anti-Ki67 antibody, an anti-5-bromo-2'-deoxyuridine (BrdU) antibody, and an anti-cyclin D1 antibody. Positive cells stained by the 4 antibodies were identified mainly in the basal layer. The mean numbers of positive cells stained by the 4 antibodies in 500 olfactory epithelium cells from each animal were as follows: PCNA-positive cells 42, Ki67-positive cells 23, BrdU-positive cells 13.7, and cyclin D1-positive cells 9.2. PCNA may be detected in both proliferating and resting cells. Ki67 is an intranuclear antigen expressed in proliferating, but not resting, cells. Anti-BrdU antibodies might stain proliferating cells only following the S-phase, but not the G1-phase. Cyclin D1 is a protein that works during the G1-phase of the cell cycle. When we stain proliferating cells using proliferating cell markers, it is important to consider the cell cycle phases during which each marker stains.