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 MKI67gene (antigen identified by monoclonal antibody Ki-67).[5][6][7]
Antigen KI-67 is a nuclear protein that is associated with cellular proliferation and ribosomal RNA transcription.[7] Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis,[8] but does not significantly affect cell proliferation in vivo: Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently.[9]
The Ki-67 protein (also known as MKI67) is a cellular marker for proliferation,[10] 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.[11] 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).[12] Cellular content of Ki-67 protein markedly increases during cell progression through S phase of the cell cycle.[13] In breast cancer Ki67 identifies a high proliferative subset of patients with ER-positive breast cancer who derive greater benefit from adjuvant chemotherapy.[14][15]
Antibody labelingedit
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-1edit
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.[16] 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).
High Ki-67 expression in an invasive breast cancer, with cancer nuclei being stained (brown). There is tumor cell positivity in 70% of the cells: Ki-67 labelling index = 70%
Counting positive versus negative nuclei with Ki-67 labeling, in this case in a neuroendocrine tumor of the small intestine. To count as positive, a nucleus should be at least half within the field of view, be large enough, and not be located in the stroma. Otherwise, even weakly positive nuclei count as positive.
Original Ki-67 antibodyedit
The Ki-67 protein was originally defined by the prototype monoclonal antibody Ki-67,[17] 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.
PCNA - Proliferating Cell Nuclear Antigen, expressed during the DNA synthesis.
Additional imagesedit
Immunofluorescent antibody staining against neurofilament (green) and Ki-67 (red) in a mouse embryo 12.5 days after fertilization. The proliferating cells are in the ventricular zone in the neural tube and therefore colored red.
Protein Ki-67 in human MCF-7 cells
Ki-67 protein (red), tubulin (green) and DNA (blue) in HeLa cells. Dividing cells show strong Ki-67 staining in cell nuclei while all cells contain large amounts of tubulin, the major component of microtubules. Antibodies, cell staining and image courtesy of EnCor Biotechnology.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000148773 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000031004 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Entrez Gene: Antigen identified by monoclonal antibody Ki-67".
^Schonk DM, Kuijpers HJ, van Drunen E, van Dalen CH, Geurts van Kessel AH, Verheijen R, Ramaekers FC (October 1989). "Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10". Hum. Genet. 83 (3): 297–9. doi:10.1007/BF00285178. PMID 2571566. S2CID 32117144.
^ abBullwinkel J, Baron-Lühr B, Lüdemann A, Wohlenberg C, Gerdes J, Scholzen T (March 2006). "Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells". J. Cell. Physiol. 206 (3): 624–35. doi:10.1002/jcp.20494. PMID 16206250. S2CID 22770145.
^Rahmanzadeh R, Hüttmann G, Gerdes J, Scholzen T (June 2007). "Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis". Cell Prolif. 40 (3): 422–30. doi:10.1111/j.1365-2184.2007.00433.x. PMC6496591. PMID 17531085.
^Sobecki M, Mrouj K, Camasses A, Parisis N, Nicolas E, Llères D, Gerbe F, Prieto S, Krasinska L, David A, others (Mar 6, 2016). "The cell proliferation antigen Ki-67 organises heterochromatin". eLife. 5 (e13722): e13722. doi:10.7554/eLife.13722. PMC4841783. PMID 26949251.
^Scholzen T, Gerdes J (March 2000). "The Ki-67 protein: from the known and the unknown". Journal of Cellular Physiology. 182 (3): 311–22. doi:10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9. PMID 10653597. S2CID 22944989.
^Cuylen S, Blaukopf C, Politi AZ, Müller-Reichert T, Neumann B, Poser I, Ellenberg J, Hyman AA, Gerlich DW (July 2016). "Ki-67 acts as a biological surfactant to disperse mitotic chromosomes". Nature. 535 (7611): 308–12. Bibcode:2016Natur.535..308C. doi:10.1038/nature18610. PMC4947524. PMID 27362226.
^Bruno S, Darzynkiewicz Z (January 1992). "Cell cycle dependent expression and stability of the nuclear protein detected by Ki-67 antibody in HL-60 cells". Cell Proliferation. 25 (1): 31–40. doi:10.1111/j.1365-2184.1992.tb01435.x. PMID 1540682. S2CID 37050410.
^Darzynkiewicz Z, Zhao H, Zhang S, Lee MY, Lee EY, Zhang Z (May 2015). "Initiation and termination of DNA replication during S phase in relation to cyclins D1, E and A, p21WAF1, Cdt1 and the p12 subunit of DNA polymerase δ revealed in individual cells by cytometry". Oncotarget. 6 (14): 11735–50. doi:10.18632/oncotarget.4149. PMC4494901. PMID 26059433.
^Sonnenblick A, Francis PA, Azim HA, de Azambuja E, Nordenskjöld B, Gutiérez J, Quinaux E, Mastropasqua MG, Ameye L, Anderson M, Lluch A, Gnant M, Goldhirsch A, Di Leo A, Barnadas A, Cortes-Funes H, Piccart M, Crown J (2015). "Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer". European Journal of Cancer. 51 (12): 1481–9. doi:10.1016/j.ejca.2015.03.018. PMID 26074397.
^Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA (2010). "Ki67 in breast cancer: prognostic and predictive potential". The Lancet. Oncology. 11 (2): 174–83. doi:10.1016/S1470-2045(09)70262-1. PMID 20152769.
^Bánkfalvi A (November 2000). "Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use". Histopathology. 37 (5): 411–9. doi:10.1046/j.1365-2559.2000.00984.x. PMID 11119122. S2CID 35267896.
^Gerdes J, Schwab U, Lemke H, Stein H (1983). "Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation". Int. J. Cancer. 31 (1): 13–20. doi:10.1002/ijc.2910310104. PMID 6339421. S2CID 1764319.
^Kametaka A, Takagi M, Hayakawa T, Haraguchi T, Hiraoka Y, Yoneda Y (2002). "Interaction of the chromatin compaction-inducing domain (LR domain) of Ki-67 antigen with HP1 proteins". Genes to Cells. 7 (12): 1231–42. doi:10.1046/j.1365-2443.2002.00596.x. PMID 12485163. S2CID 6802841.
Overview of all the structural information available in the PDB for UniProt: P46013 (Proliferation marker protein Ki-67) at the PDBe-KB.
January 01, 1970
protein, japanese, bomber, mitsubishi, antigen, kiel, also, known, mki67, marker, proliferation, kiel, protein, that, humans, encoded, mki67, gene, antigen, identified, monoclonal, antibody, mki67available, structurespdbortholog, search, pdbe, rcsblist, codes1. For the Japanese bomber see Mitsubishi Ki 67 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 5 6 7 MKI67Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1R21 2AFFIdentifiersAliasesMKI67 marker of proliferation Ki 67 KIA MIB MIB 1 PPP1R105External IDsOMIM 176741 MGI 106035 HomoloGene 1814 GeneCards MKI67Gene location Human Chr Chromosome 10 human 1 Band10q26 2Start128 096 659 bp 1 End128 126 423 bp 1 Gene location Mouse Chr Chromosome 7 mouse 2 Band7 7 F3Start135 291 513 bp 2 End135 318 090 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inganglionic eminencebone marrow cellstrabecular bonethymusstromal cell of endometriumrectumappendixlymph nodeoral cavityepithelium of esophagusTop expressed inPaneth cellvas deferenshair follicleprimitive streakhanddermisfossacondylemaxillary prominenceinternal carotid arteryMore reference expression dataBioGPSn aGene ontologyMolecular functionnucleotide binding protein C terminus binding protein binding ATP binding DNA binding RNA bindingCellular componentcytoplasm membrane chromosome nucleolus chromosome centromeric region nucleus condensed chromosome nuclear bodyBiological processcellular response to heat response to organic cyclic compound DNA metabolic process animal organ regeneration hyaluronan metabolic process cell cycle regulation of chromosome segregation cell population proliferation regulation of mitotic nuclear division regulation of chromatin organization meiosisSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez428817345EnsemblENSG00000148773ENSMUSG00000031004UniProtP46013E9PVX6RefSeq mRNA NM 001145966NM 002417NM 001081117RefSeq protein NP 001139438NP 002408NP 001074586Location UCSC Chr 10 128 1 128 13 MbChr 7 135 29 135 32 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Use as a marker of proliferating cells 3 Antibody labeling 3 1 MIB 1 3 2 Original Ki 67 antibody 4 Interactions 5 See also 6 Additional images 7 References 8 External linksFunction editAntigen KI 67 is a nuclear protein that is associated with cellular proliferation and ribosomal RNA transcription 7 Inactivation of antigen KI 67 leads to inhibition of ribosomal RNA synthesis 8 but does not significantly affect cell proliferation in vivo Ki 67 mutant mice developed normally and cells lacking Ki 67 proliferated efficiently 9 Use as a marker of proliferating cells edit nbsp Ki 67 immunostaining of a brain tumour with a high proliferative rate The Ki 67 protein also known as MKI67 is a cellular marker for proliferation 10 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 11 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 12 Cellular content of Ki 67 protein markedly increases during cell progression through S phase of the cell cycle 13 In breast cancer Ki67 identifies a high proliferative subset of patients with ER positive breast cancer who derive greater benefit from adjuvant chemotherapy 14 15 Antibody labeling editKi 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 edit 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 16 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 nbsp High Ki 67 expression in an invasive breast cancer with cancer nuclei being stained brown There is tumor cell positivity in 70 of the cells Ki 67 labelling index 70 nbsp Counting positive versus negative nuclei with Ki 67 labeling in this case in a neuroendocrine tumor of the small intestine To count as positive a nucleus should be at least half within the field of view be large enough and not be located in the stroma Otherwise even weakly positive nuclei count as positive Original Ki 67 antibody edit The Ki 67 protein was originally defined by the prototype monoclonal antibody Ki 67 17 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 editKi 67 protein has been shown to interact with CBX3 18 See also editPCNA Proliferating Cell Nuclear Antigen expressed during the DNA synthesis Additional images edit nbsp Immunofluorescent antibody staining against neurofilament green and Ki 67 red in a mouse embryo 12 5 days after fertilization The proliferating cells are in the ventricular zone in the neural tube and therefore colored red nbsp Protein Ki 67 in human MCF 7 cells nbsp Ki 67 protein red tubulin green and DNA blue in HeLa cells Dividing cells show strong Ki 67 staining in cell nuclei while all cells contain large amounts of tubulin the major component of microtubules Antibodies cell staining and image courtesy of EnCor Biotechnology References edit a b c GRCh38 Ensembl release 89 ENSG00000148773 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000031004 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Entrez Gene Antigen identified by monoclonal antibody Ki 67 Schonk DM Kuijpers HJ van Drunen E van Dalen CH Geurts van Kessel AH Verheijen R Ramaekers FC October 1989 Assignment of the gene s involved in the expression of the proliferation related Ki 67 antigen to human chromosome 10 Hum Genet 83 3 297 9 doi 10 1007 BF00285178 PMID 2571566 S2CID 32117144 a b Bullwinkel J Baron Luhr B Ludemann A Wohlenberg C Gerdes J Scholzen T March 2006 Ki 67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells J Cell Physiol 206 3 624 35 doi 10 1002 jcp 20494 PMID 16206250 S2CID 22770145 Rahmanzadeh R Huttmann G Gerdes J Scholzen T June 2007 Chromophore assisted light inactivation of pKi 67 leads to inhibition of ribosomal RNA synthesis Cell Prolif 40 3 422 30 doi 10 1111 j 1365 2184 2007 00433 x PMC 6496591 PMID 17531085 Sobecki M Mrouj K Camasses A Parisis N Nicolas E Lleres D Gerbe F Prieto S Krasinska L David A others Mar 6 2016 The cell proliferation antigen Ki 67 organises heterochromatin eLife 5 e13722 e13722 doi 10 7554 eLife 13722 PMC 4841783 PMID 26949251 Scholzen T Gerdes J March 2000 The Ki 67 protein from the known and the unknown Journal of Cellular Physiology 182 3 311 22 doi 10 1002 SICI 1097 4652 200003 182 3 lt 311 AID JCP1 gt 3 0 CO 2 9 PMID 10653597 S2CID 22944989 Cuylen S Blaukopf C Politi AZ Muller Reichert T Neumann B Poser I Ellenberg J Hyman AA Gerlich DW July 2016 Ki 67 acts as a biological surfactant to disperse mitotic chromosomes Nature 535 7611 308 12 Bibcode 2016Natur 535 308C doi 10 1038 nature18610 PMC 4947524 PMID 27362226 Bruno S Darzynkiewicz Z January 1992 Cell cycle dependent expression and stability of the nuclear protein detected by Ki 67 antibody in HL 60 cells Cell Proliferation 25 1 31 40 doi 10 1111 j 1365 2184 1992 tb01435 x PMID 1540682 S2CID 37050410 Darzynkiewicz Z Zhao H Zhang S Lee MY Lee EY Zhang Z May 2015 Initiation and termination of DNA replication during S phase in relation to cyclins D1 E and A p21WAF1 Cdt1 and the p12 subunit of DNA polymerase d revealed in individual cells by cytometry Oncotarget 6 14 11735 50 doi 10 18632 oncotarget 4149 PMC 4494901 PMID 26059433 Sonnenblick A Francis PA Azim HA de Azambuja E Nordenskjold B Gutierez J Quinaux E Mastropasqua MG Ameye L Anderson M Lluch A Gnant M Goldhirsch A Di Leo A Barnadas A Cortes Funes H Piccart M Crown J 2015 Final 10 year results of the Breast International Group 2 98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer European Journal of Cancer 51 12 1481 9 doi 10 1016 j ejca 2015 03 018 PMID 26074397 Yerushalmi R Woods R Ravdin PM Hayes MM Gelmon KA 2010 Ki67 in breast cancer prognostic and predictive potential The Lancet Oncology 11 2 174 83 doi 10 1016 S1470 2045 09 70262 1 PMID 20152769 Bankfalvi A November 2000 Comparative methodological analysis of erbB 2 HER 2 gene dosage chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use Histopathology 37 5 411 9 doi 10 1046 j 1365 2559 2000 00984 x PMID 11119122 S2CID 35267896 Gerdes J Schwab U Lemke H Stein H 1983 Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation Int J Cancer 31 1 13 20 doi 10 1002 ijc 2910310104 PMID 6339421 S2CID 1764319 Kametaka A Takagi M Hayakawa T Haraguchi T Hiraoka Y Yoneda Y 2002 Interaction of the chromatin compaction inducing domain LR domain of Ki 67 antigen with HP1 proteins Genes to Cells 7 12 1231 42 doi 10 1046 j 1365 2443 2002 00596 x PMID 12485163 S2CID 6802841 External links editKi 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 Retrieved from https en wikipedia org w index php title Ki 67 protein amp oldid 1188034634, wikipedia, wiki, book, books, library,
