Antigen KI-67 also known as Ki-67 or MKI67 is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the MKI67 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 (antigen identified by monoclonal antibody Ki-67).

Function

Antigen KI-67 is a nuclear protein that is associated with and may be necessary for cellular proliferation. Furthermore it is associated with ribosomal RNA

Ribosomal RNA

Ribosomal ribonucleic acid is the RNA component of the ribosome, the enzyme that is the site of protein synthesis in all living cells. Ribosomal RNA provides a mechanism for decoding mRNA into amino acids and interacts with tRNAs during translation by providing peptidyl transferase activity...

 transcription. Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis.

Use as cell marker

The Ki-67 protein (also known as MKI67) is a cellular marker for proliferation. It is strictly associated with cell proliferation. During interphase

Interphase

Interphase is the phase of the cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for cell division. In preparation for cell division, it increases its size and makes a copy of its DNA...

, the Ki-67 antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

 can be exclusively detected within the cell nucleus

Cell nucleus

In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

, whereas in mitosis

Mitosis

Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 most of the protein is relocated to the surface of the chromosome

Chromosome

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

s. Ki-67 protein is present during all active phases of the cell cycle

Cell cycle

The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

 (G₁, S, G₂, and mitosis), but is absent from resting cells (G₀).

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

Tumor

A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. The best-studied examples in this context are carcinoma

Carcinoma

Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...

s of the prostate

Prostate

The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....

, brain

Brain

The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 and the breast

Breast

The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...

. For these types of tumors, the prognostic value for survival and tumor recurrence have repeatedly been proven in uni- and multivariate analysis.

MIB-1

MIB-1 is a commonly used monoclonal antibody that detects the Ki-67 antigen. It 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 section Original Ki-67 antibody).

Original Ki-67 antibody

The Ki-67 protein was originally defined by the prototype monoclonal antibody

Antibody

An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 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

Kiel

Kiel is the capital and most populous city in the northern German state of Schleswig-Holstein, with a population of 238,049 .Kiel is approximately north of Hamburg. Due to its geographic location in the north of Germany, the southeast of the Jutland peninsula, and the southwestern shore of the...

, Germany) and the number of the original clone in the 96-well plate.

Interactions

Ki-67 (protein) has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with CBX3

CBX3

Chromobox protein homolog 3 is a protein that in humans is encoded by the CBX3 gene.-Interactions:CBX3 has been shown to interact with PIM1, Ki-67, Lamin B receptor, CBX5 and CBX1....

.

See also

• PCNA
  PCNA
  Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a protein that acts as a processivity factor for DNA polymerase δ in eukaryotic cells. It achieves this processivity by encircling the DNA, thus creating a topological link to the genome...
  
  - Proliferating Cell Nuclear Antigen, expressed during the DNA synthesis.