Ki-67 (protein)

Antigen Kiel 67, also known as Ki-67 or MKI67 (marker of proliferation Kiel 67), is a protein that in humans is encoded by the MKI67 gene (antigen identified by monoclonal antibody Ki-67).

Function

Antigen KI-67 is a nuclear protein that is associated with cellular proliferation and ribosomal RNA transcription. Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis, but does not significantly affect cell proliferation in vivo: Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently.

Use as a marker of proliferating cells

The Ki-67 protein (also known as MKI67) is a cellular marker for proliferation, and can be used in immunohistochemistry. It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G₁, S, G₂, and mitosis), but is absent in resting (quiescent) cells (G₀). Cellular content of Ki-67 protein markedly increases during cell progression through S phase of the cell cycle. In breast cancer Ki67 identifies a high proliferative subset of patients with ER-positive breast cancer who derive greater benefit from adjuvant chemotherapy.

Antibody labeling

Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. The best-studied examples in this context are prostate, brain and breast carcinomas, as well as nephroblastoma and neuroendocrine tumors. For these types of tumors, the prognostic value for survival and tumor recurrence have repeatedly been proven in uni- and multivariate analysis.

MIB-1

Ki-67 and MIB-1 monoclonal antibodies are directed against different epitopes of the same proliferation-related antigen. Ki-67 and MIB-1 may be used on fixed sections. MIB-1 is used in clinical applications to determine the Ki-67 labelling index. One of its primary advantages over the original Ki-67 antibody (and the reason why it has essentially supplanted the original antibody for clinical use) is that it can be used on formalin-fixed paraffin-embedded sections, after heat-mediated antigen retrieval (see next section below).

Original Ki-67 antibody

The Ki-67 protein was originally defined by the prototype monoclonal antibody Ki-67, which was generated by immunizing mice with nuclei of the Hodgkin lymphoma cell line L428. The name is derived from the city of origin (Kiel, Germany) and the number of the original clone in the 96-well plate.

Interactions

Ki-67 (protein) has been shown to interact with CBX3.

See also

• PCNA - Proliferating Cell Nuclear Antigen, expressed during the DNA synthesis.

Additional images

References

External links

• Ki-67+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• http://www.pathologyoutlines.com/topic/stainski67.html
• Overview of all the structural information available in the PDB for UniProt: P46013 (Proliferation marker protein Ki-67) at the PDBe-KB.

1. Ki-67
2. Invasive cribriform carcinoma of the breast
3. Indolent T cell lymphoproliferative disorder of the gastrointestinal tract
4. Natural killer cell enteropathy
5. CBX3
6. Pure apocrine carcinoma of the breast
7. CBX1
8. CBX5 (gene)
9. Green fluorescent protein
10. Protein toxicity
11. ABCC11
12. Uromodulin
13. HD-6277
14. Ubiquitin ligase
15. MIB1
16. Proliferative index
17. Enzyme inhibitor
18. Multiple myeloma
19. Chlorphenamine
20. CD68