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Gene Review

Mki67  -  antigen identified by monoclonal antibody...

Mus musculus

Synonyms: D630048A14Rik, Ki-67, Ki67
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Disease relevance of Mki67

  • Moreover, in HCV-infected livers with cirrhosis, activation of STAT1 was detected and correlated positively with liver injury (elevated serum levels of AST) but negatively with hepatocyte proliferation (hepatocyte PCNA and Ki-67 positive immunostaining) [1].
  • RESULTS: In thrombocytotic and thrombocytopenic mice, liver/body weight ratios and Ki-67 labeling indices were significantly increased and significantly decreased, respectively, compared with untreated mice 48 hours post-hepatectomy [2].
  • Selected adenomas were assessed for proliferative activity by Ki-67 immunocytochemistry [3].
  • In all samples tested, overexpression of Ki-67 antigen was shown by immunohistochemistry, indicating a high proliferative index of SCID mice EBV-induced lymphoproliferation [4].
  • MMPs, VEGF, Ki-67 (proliferative protein), and constituents of ECM play a critical role in angiogenesis and underlie neoplastic invasion and metastasis [5].

Psychiatry related information on Mki67

  • Additionally, after therapy, Ki67 index showed >4-fold reduction of tumor proliferation in the combination therapy group, which also showed increased intratumoral apoptotic index by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining [6].

High impact information on Mki67

  • In contrast, analysis of the A/WySnJ GC response revealed a B cell autonomous proliferative defect associated with reduced or undetectable Ki67 nuclear proliferation antigen expression by GC B cells at all stages of the response [7].
  • Immunohistochemical analysis using lymphatic-specific markers: VEGFR-3, lymphatic endothelial hyaluronan receptor-1, together with the proliferation marker Ki-67 Ab revealed that phVEGF-C transfection potently induced new lymphatic vessel growth [8].
  • The rapid effect of hormone deprivation and resubstitution in the tumor cell proliferation fraction suggests that monoclonal antibody Ki-67 can be used for monitoring the short-term effects of hormonal treatment of prostatic cancer [9].
  • The number of Ki-67-positive tumor cells dropped from an average of 17% in androgen-supplemented, tumor-bearing female BALB/c mice to approximately 1.0% within 10 days after removal of the testosterone (T) implant [9].
  • Administration of supraphysiologic doses of T in intact male mice did not lead to an increase in the number of Ki-67-stained nuclei [9].

Chemical compound and disease context of Mki67


Biological context of Mki67

  • Assignment1 of the murine Ki-67 gene (Mki67) to chromosome band 7F3-F5 by in situ hybridization [13].
  • This phenotype depended on COX-2-mediated PGE(2) synthesis and correlated with increased expression of proliferation-associated Ki67 in epithelial cells [14].
  • Here, we show p63 expression during teeth and vibrissae morphogenesis in mouse embryos and we also show a correlation with the expression patterns of the epithelial marker keratin 5 and the proliferation marker Ki67 [15].
  • In contrast, anterior pituitaries of Cdk4-null mice at postnatal 8 weeks are extremely hypoplastic with markedly decreased numbers of Ki67+ cells, suggesting impaired cell proliferation [16].
  • The murine Ki-67 cDNA sequence (TSG126) was found to contain 13 tandem repeats, making up more than half of the total protein size [17].

Anatomical context of Mki67

  • The Ki-67 protein reappeared in oocytes of growing follicles and was continuously present up to metaphase II [18].
  • Expression of beta-catenin was examined together with the expression of Ki-67, a marker for proliferating cells, or myosin VIIa, a marker for differentiated hair cells [19].
  • Proliferation was assessed in cultured cells and tissue by (3)H-thymidine incorporation and Ki-67 immunostaining, respectively [20].
  • Furthermore, in human failing and nonfailing hearts, similar observations were documented including induction of active caspase 3 and Ki-67 proteins in dilated cardiomyopathic myocytes [21].
  • The aim of the present study was to examine age-related changes in the proliferative capacity of acinar and ductal cells in labial salivary glands of healthy subjects as reflected by AgNOR and Ki-67 parameters [22].

Associations of Mki67 with chemical compounds

  • Interestingly, the G(0) cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells [23].
  • FACS analysis showed that the cells strongly positive for SSEA-1 co-expressed Ki67 proliferation antigen in all the developmental stages examined [24].
  • JTE-522 decreased COX-2 expression and Ki67 labeling index within the coinoculated tumor [25].
  • Although the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling method revealed few apoptotic nuclei, the number of proliferating cells was significantly decreased (Ki-67 antigen study) [26].
  • Testosterone treatment from 21 to 28 days post-castration resulted in an increase in Ki-67 antigen positive cells to 200% of intact controls and a concomitant reduction in p27 expressing cells to about 50% of intact controls [27].

Co-localisations of Mki67

  • Moreover, p63 expression in tooth seems not to be fully colocalized with nuclear Ki67 expression [15].

Regulatory relationships of Mki67

  • In the present study, we demonstrate that treatment of embryoid bodies grown from pluripotent murine embryonic stem (ES) cells with CT-1 significantly stimulated cardiomyogenesis and increased nuclear expression of the proliferation marker Ki-67 [28].

Other interactions of Mki67

  • In order to do this we used nestin-EGFP and TLX-LacZ transgenic mice, as well as labeling for Ki67, a marker for dividing cells [29].
  • The rapid appearance of these tumors from a relatively small pool of infected cells (estimated to be approximately 2 x 10(3) cells per gland by infection with RCAS carrying a GFP gene; RCAS-GFP) was accompanied by a high fraction of cells positive for Ki67, Cyclin D1, and c-Myc, implying strong proliferation competence [30].
  • The proliferative effect of SB216763 was attenuated by an FGF receptor inhibitor but was enhanced by FGF2, with Ki-67-positive cells reaching over 70% of the total cells [31].
  • Wnt3a increased the size of the primary spheres and the number of Ki-67-positive proliferating cells in monolayer culture [31].
  • Growth kinetics in the liver were analyzed as a function of the liver/body weight ratio, the mitotic index, the proliferating cell nuclear antigen labeling index and Ki-67 labeling index [2].

Analytical, diagnostic and therapeutic context of Mki67

  • The tumors were analyzed by immunohistochemistry for expression of Ki-67, tissue transglutaminase, and vascular endothelial growth factor [32].
  • Microscopic analysis of the xenograft tumors revealed a reduced Ki-67 labeling and a lower amount of tumor necrosis in FGFR1-IIIb-expressing tumors [33].
  • Immunofluorescence staining of cells coexpressing ras and E6 from either HPV16 or HPV1 revealed that antiproliferative (p16(INK4a)) and proliferative (Ki67) markers were coexpressed in the same cells [34].
  • Concomitant with this, expression of Ki-67, p53 and bcl-2 proteins was increased, and apoptotic cells were decreased as demonstrated by the TUNEL method [35].
  • The average labeling index (LI) for Ki-67 in SRRS group was significantly decreased to 8.43+/-2.22 % compared with the control group (10.37+/-4.91 %) (P<0.05) [36].


  1. STAT1 contributes to dsRNA inhibition of liver regeneration after partial hepatectomy in mice. Sun, R., Park, O., Horiguchi, N., Kulkarni, S., Jeong, W.I., Sun, H.Y., Radaeva, S., Gao, B. Hepatology (2006) [Pubmed]
  2. Platelets promote liver regeneration in early period after hepatectomy in mice. Murata, S., Ohkohchi, N., Matsuo, R., Ikeda, O., Myronovych, A., Hoshi, R. World journal of surgery (2007) [Pubmed]
  3. Analysis of chromosomal instability in human colorectal adenomas with two mutational hits at APC. Sieber, O.M., Heinimann, K., Gorman, P., Lamlum, H., Crabtree, M., Simpson, C.A., Davies, D., Neale, K., Hodgson, S.V., Roylance, R.R., Phillips, R.K., Bodmer, W.F., Tomlinson, I.P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  4. High expression of MDM2 protein and low rate of p21(WAF1/CIP1) expression in SCID mice Epstein Barr virus-induced lymphoproliferation. El Mansouri, S., Martin, A., Mercadier, A., Capoulade, C., Maréchal, V., Wiels, J., Feuillard, J., Raphaël, M. J. Histochem. Cytochem. (1999) [Pubmed]
  5. Effect of Ascorbic Acid, Lysine, Proline, and Green Tea Extract on Human Osteosarcoma Cell Line MNNG-HOS Xenografts in Nude Mice: Evaluation of Tumor Growth and Immunohistochemistry. Roomi, M.W., Ivanov, V., Kalinovsky, T., Niedzwiecki, A., Rath, M. Med. Oncol. (2006) [Pubmed]
  6. Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor AZD2171 and Fractionated Radiotherapy in Mouse Models of Lung Cancer. Cao, C., Albert, J.M., Geng, L., Ivy, P.S., Sandler, A., Johnson, D.H., Lu, B. Cancer Res. (2006) [Pubmed]
  7. Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling-deficient mice. Rahman, Z.S., Rao, S.P., Kalled, S.L., Manser, T. J. Exp. Med. (2003) [Pubmed]
  8. VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema. Yoon, Y.S., Murayama, T., Gravereaux, E., Tkebuchava, T., Silver, M., Curry, C., Wecker, A., Kirchmair, R., Hu, C.S., Kearney, M., Ashare, A., Jackson, D.G., Kubo, H., Isner, J.M., Losordo, D.W. J. Clin. Invest. (2003) [Pubmed]
  9. Determination of the proliferative fraction of a transplantable, hormone-dependent, human prostatic carcinoma (PC-82) by monoclonal antibody Ki-67: potential application for hormone therapy monitoring. Gallee, M.P., van Steenbrugge, G.J., ten Kate, F.J., Schroeder, F.H., van der Kwast, T.H. J. Natl. Cancer Inst. (1987) [Pubmed]
  10. Angiotensin II Type 1 Receptor Blockade Inhibits the Development and Progression of HIV-Associated Nephropathy in a Mouse Model. Hiramatsu, N., Hiromura, K., Shigehara, T., Kuroiwa, T., Ideura, H., Sakurai, N., Takeuchi, S., Tomioka, M., Ikeuchi, H., Kaneko, Y., Ueki, K., Kopp, J.B., Nojima, Y. J. Am. Soc. Nephrol. (2007) [Pubmed]
  11. Androgen withdrawal inhibits tumor growth and is associated with decrease in angiogenesis and VEGF expression in androgen-independent CWR22Rv1 human prostate cancer model. Cheng, L., Zhang, S., Sweeney, C.J., Kao, C., Gardner, T.A., Eble, J.N. Anticancer Res. (2004) [Pubmed]
  12. Expression of Ki-67--a proliferation-associated antigen--in prostatic cancer. Nilsson, S., Nordgren, H., Eklöv, S., Lögdahl, M. Acta oncologica (Stockholm, Sweden) (1991) [Pubmed]
  13. Assignment1 of the murine Ki-67 gene (Mki67) to chromosome band 7F3-F5 by in situ hybridization. Traut, W., Scholzen, T., Winking, H., Kubbutat, M.H., Gerdes, J. Cytogenet. Cell Genet. (1998) [Pubmed]
  14. Cystic duct dilatations and proliferative epithelial lesions in mouse mammary glands upon keratin 5 promoter-driven overexpression of cyclooxygenase-2. Müller-Decker, K., Berger, I., Ackermann, K., Ehemann, V., Zoubova, S., Aulmann, S., Pyerin, W., Fürstenberger, G. Am. J. Pathol. (2005) [Pubmed]
  15. p63 protein is essential for the embryonic development of vibrissae and teeth. Rufini, A., Weil, M., McKeon, F., Barlattani, A., Melino, G., Candi, E. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  16. Cdk4 is indispensable for postnatal proliferation of the anterior pituitary. Jirawatnotai, S., Aziyu, A., Osmundson, E.C., Moons, D.S., Zou, X., Kineman, R.D., Kiyokawa, H. J. Biol. Chem. (2004) [Pubmed]
  17. The murine Ki-67 cell proliferation antigen accumulates in the nucleolar and heterochromatic regions of interphase cells and at the periphery of the mitotic chromosomes in a process essential for cell cycle progression. Starborg, M., Gell, K., Brundell, E., Höög, C. J. Cell. Sci. (1996) [Pubmed]
  18. The temporal and spatial distribution of the proliferation associated Ki-67 protein during female and male meiosis. Traut, W., Endl, E., Scholzen, T., Gerdes, J., Winking, H. Chromosoma (2002) [Pubmed]
  19. Expression of beta-catenin in developing auditory epithelia of mice. Takebayashi, S., Nakagawa, T., Kojima, K., Kim, T.S., Kita, T., Dong, Y., Endo, T., Iguchi, F., Naito, Y., Omori, K., Ito, J. Acta oto-laryngologica. Supplementum. (2004) [Pubmed]
  20. Regulation of p53 by macrophage migration inhibitory factor in inflammatory arthritis. Leech, M., Lacey, D., Xue, J.R., Santos, L., Hutchinson, P., Wolvetang, E., David, J.R., Bucala, R., Morand, E.F. Arthritis Rheum. (2003) [Pubmed]
  21. Myocardial cell death and regeneration during progression of cardiac hypertrophy to heart failure. Sarkar, S., Chawla-Sarkar, M., Young, D., Nishiyama, K., Rayborn, M.E., Hollyfield, J.G., Sen, S. J. Biol. Chem. (2004) [Pubmed]
  22. Age-related changes in proliferative markers in labial salivary glands: a study of argyrophilic nucleolar organizer regions (AgNORs) and Ki-67. Dayan, D., Vered, M., Sivor, S., Hiss, Y., Buchner, A. Exp. Gerontol. (2002) [Pubmed]
  23. Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G(2)/M transit and do not reenter G(0). Glimm, H., Oh, I.H., Eaves, C.J. Blood (2000) [Pubmed]
  24. SSEA-1 marks regionally restricted immature subpopulations of embryonic retinal progenitor cells that are regulated by the Wnt signaling pathway. Koso, H., Ouchi, Y., Tabata, Y., Aoki, Y., Satoh, S., Arai, K., Watanabe, S. Dev. Biol. (2006) [Pubmed]
  25. Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial-mesenchymal interactions of growth in scirrhous gastric carcinoma. Yashiro, M., Nakazawa, K., Tendo, M., Kosaka, K., Shinto, O., Hirakawa, K. Int. J. Cancer (2007) [Pubmed]
  26. Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer: implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase. Quidville, V., Segond, N., Pidoux, E., Cohen, R., Jullienne, A., Lausson, S. Endocrinology (2004) [Pubmed]
  27. Changes in cyclin dependent kinase inhibitors p21 and p27 during the castration induced regression of the CWR22 model of prostatic adenocarcinoma. Myers, R.B., Oelschlager, D.K., Coan, P.N., Frost, A.R., Weiss, H.L., Manne, U., Pretlow, T.G., Grizzle, W.E. J. Urol. (1999) [Pubmed]
  28. Involvement of reactive oxygen species in cardiotrophin-1-induced proliferation of cardiomyocytes differentiated from murine embryonic stem cells. Sauer, H., Neukirchen, W., Rahimi, G., Grünheck, F., Hescheler, J., Wartenberg, M. Exp. Cell Res. (2004) [Pubmed]
  29. Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain. Tran, P.B., Banisadr, G., Ren, D., Chenn, A., Miller, R.J. J. Comp. Neurol. (2007) [Pubmed]
  30. Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models. Du, Z., Podsypanina, K., Huang, S., McGrath, A., Toneff, M.J., Bogoslovskaia, E., Zhang, X., Moraes, R.C., Fluck, M., Allred, D.C., Lewis, M.T., Varmus, H.E., Li, Y. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  31. Activation of canonical Wnt pathway promotes proliferation of retinal stem cells derived from adult mouse ciliary margin. Inoue, T., Kagawa, T., Fukushima, M., Shimizu, T., Yoshinaga, Y., Takada, S., Tanihara, H., Taga, T. Stem Cells (2006) [Pubmed]
  32. Regulation of growth of prostate cancer cells selected in the presence of interleukin-6 by the anti-interleukin-6 antibody CNTO 328. Steiner, H., Cavarretta, I.T., Moser, P.L., Berger, A.P., Bektic, J., Dietrich, H., Zaki, M.H., Nakada, M., Hobisch, A., Nemeth, J.A., Culig, Z. Prostate (2006) [Pubmed]
  33. Identification of a fibroblast growth factor receptor 1 splice variant that inhibits pancreatic cancer cell growth. Liu, Z., Neiss, N., Zhou, S., Henne-Bruns, D., Korc, M., Bachem, M., Kornmann, M. Cancer Res. (2007) [Pubmed]
  34. Human papillomavirus type 16 E6 promotes retinoblastoma protein phosphorylation and cell cycle progression. Malanchi, I., Accardi, R., Diehl, F., Smet, A., Androphy, E., Hoheisel, J., Tommasino, M. J. Virol. (2004) [Pubmed]
  35. Changes of histological and biological features by serial passages in a human adenoid cystic carcinoma line transplantable in nude mice. Hashitani, S., Noguchi, K., Manno, Y., Moridera, K., Takaoka, K., Nishimura, N., Kishimoto, H., Sakurai, K., Urade, M. Oncol. Rep. (2005) [Pubmed]
  36. Effects of Chinese Jianpi herbs on cell apoptosis and related gene expression in human gastric cancer grafted onto nude mice. Zhao, A.G., Zhao, H.L., Jin, X.J., Yang, J.K., Tang, L.D. World J. Gastroenterol. (2002) [Pubmed]
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