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Gene Review

F12  -  coagulation factor XII (Hageman factor)

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Disease relevance of F12

  • The addition of 1 percent (w/v) bovine serum albumin (BSA) to the F12 medium utilized for the growth of the B16 melanoma cells significantly stimulated the growth of this cell line [1].
  • 3. F12 media containing the purified BSA plus selenite and the sodium salts of palmitic, oleic, and linoleic acids supported growth of the melanoma cells to the same extent as did the media containing unpurified BSA, indicating that the sialoglycoprotein has no role in sustaining the growth of the cells [1].
  • METHODS: The peripheral cholangiocarcinoma specimen surgically obtained from the patient was aseptically processed by washing and mincing before culturing in Ham's F12 medium containing 10% fetal bovine serum [2].
  • Highly purified bovine plasma prekallikrein was rapidly activated to kallikrein [EC] by bovine activated Hageman factor, trypsin [EC] and Pronase P (proteinases from Streptomyces griseus) and more gradually by papain [EC] and ficin [EC] [3].

High impact information on F12


Biological context of F12

  • The sequence deduced was consistent with the partial amino-acid sequences of bovine Hageman factor protein [9].
  • A bovine Hageman factor cDNA was cloned from a liver cDNA library [9].
  • These basal cells showed an exponential cell proliferation until confluence in Ham's F12 with supplements, LHC9, and a 1:1 mixture of Medium-199 and modified Eagle's medium with 2% fetal calf serum [10].
  • Jejunal explants from 5-day-old suckling rats maintained better brush border enzyme activity and better histology when cultured under hyperbaric conditions for 24 h in serum-free Dulbecco's modified Eagle's medium/F12 medium than in RPMI 1640 plus 10% fetal bovine serum [11].
  • Cell differentiation was highest (P < 0.05) in the DMEM/F12, followed by McCoy's 5A, DMEM/M-199, and BSS [12].

Anatomical context of F12

  • METHODS: FFA-free DMEM/F12, 0.125 mmol/L, 0.5 mmol/l and 1.0 mmol/L oleate or palmitate was added to cultured 3T3-L1 adipocytes or preadipocytes and incubated overnight [13].
  • Primary human bronchial epithelial cells (PBECs) were isolated from seven autopsy specimens and cultured in F12/Dulbecco's modified Eagle's medium with 5% fetal bovine serum until approximately 80% confluent [14].
  • Acinar cells were isolated from male rat lacrimal glands and cultured on Matrigel (Collaborative Research, Bedford, MA) in serum-free Dulbecco's modified Eagle's medium (DMEM)/Ham's F12 media that contained a variety of supplements [15].
  • Immunocytochemistry was performed on pUE cells cultured on several substrates (glass, serum, fibronectin, or Matrigel) in DME/F12 medium with 5% charcoal/dextran-stripped fetal bovine serum either containing no steroids or supplemented with estrogen, progesterone, or estrogen plus progesterone, or in medium with 5% complete fetal bovine serum [16].
  • Leptomeningeal and skin fetal (E16-17) fibroblasts were subcultured in vitro either in DMEM/F12 basal medium (with or without 10% FCS) or in astroglial conditioned medium (ACM) [17].

Associations of F12 with chemical compounds

  • Bovine Hageman factor has no suitable amino-acid sequence as the substrate for the trypsin-type proteinases at the proline-rich region in difference from the human and guinea pig molecules [9].
  • In two cultures of male pituitary cells maintained in DME/F12 plus ITSC, estrogen significantly elevated medium PRL levels for the 28-day period, but did not totally prevent the decline observed in control wells after day 12 [18].
  • In Dulbecco's minimum essential medium/Ham's F12 medium, 2 x 10(5) cells per well preincubated for 6 days and stimulated for 8 h resulted in large increases in melatonin (mel) release (15- to 17-fold) after adrenergic stimulation [19].
  • Isolated buds were cultured in Ham's F12 medium supplemented with epidermal growth factor, selenium, insulin, hydrocortisone, prostaglandin E1, transferrin, and triiodothyronine; fetal bovine serum (1%) was required for continuous propagation [20].
  • This was no longer the case, when the cultures were maintained in Dulbecco's modified essential medium/F12 medium to which transferrin, insulin and selenium chloride had been added [21].

Regulatory relationships of F12

  • Studies on prekallikrein of bovine plasma. II. Activation of prekallikrein with proteinases and properties of kallikrein activated by bovine Hageman factor [3].

Other interactions of F12

  • Addition of 10(-8) M estrogen to three cultures of male pituitary cells in DME/F12 containing all supplements significantly elevated PRL over control levels and, in addition, prevented the decline observed in control wells of one culture for 28 days [18].
  • Porcine open thyroid follicles obtained by treatment with 0.1% collagenase were embedded in collagen gel and cultured in Ham's F12 medium supplemented with 6H (insulin, hydrocortisone, somatostatin, transferrin, glycyl-his-lys, and thyrotropin) + 0.5% fetal bovine serum (FBS) [22].
  • Fibronectin and proteoglycan synthesis in long term cultures of cartilage explants in Ham's F12 supplemented with insulin and calcium: effects of the addition of TGF-beta [23].
  • Growth was sustained in M199/F12 (1:1) supplemented with insulin, hydrocortisone, epidermal growth factor, tri-iodothyronine, estradiol and bovine serum albumin [24].
  • Cell/polymer constructs were cultured in serum-free DMEM/F12 medium supplemented with 5 ng/mL TGF-beta2 and 5 ng/mL des(1-3)IGF-I (adult chondrocytes, group A) or in 10% FBS containing Ham's F12 medium (adult chondrocytes, group B, and fetal chondrocytes, group C) as controls in a rotating bioreactor for 6 weeks [25].

Analytical, diagnostic and therapeutic context of F12

  • Dissected tongues were maintained at the gas/liquid interface in standard organ culture dishes, fed with DMEM/F12 plus 2% B-27 supplement and 1% fetal bovine serum [26].
  • The embryonic cells sampled by biopsy or micromanipulation grow on collagen coated cover slips in Leighton tubes with Ham's F12 medium, supplemented with 20 percent fetal calf serum [27].
  • With regard to effort and outcome, the most promising group for cryopreservation was the one with DMEM/Ham's F12 plus 1% penicillin/streptomycin alone before freezing, especially when osteoblast-like cells were cultured in medium with autologous serum after thawing [28].
  • DMEM/Ham's F12 plus 1% penicillin/streptomycin with fetal bovine serum served as the control group [28].
  • In the cell culture of cryopreserved and fresh osteoblast-like cells, we substituted Dulbecco's modification of Eagle's medium (DMEM)/Ham's F12 plus 1% penicillin/streptomycin with autologous serum, human serum albumin and Biseko(R) for fetal bovine serum [28].


  1. Chemical and biological properties of B16 murine melanoma cells grown in defined medium containing bovine serum albumin. Banks, J.R., Bhavanadan, V.P., Davidson, E.A. Cancer Res. (1977) [Pubmed]
  2. Establishment and characterization of a cholangiocarcinoma cell line (RMCCA-1) from a Thai patient. Rattanasinganchan, P., Leelawat, K., Treepongkaruna, S., Tocharoentanaphol, C., Subwongcharoen, S., Suthiphongchai, T., Tohtong, R. World J. Gastroenterol. (2006) [Pubmed]
  3. Studies on prekallikrein of bovine plasma. II. Activation of prekallikrein with proteinases and properties of kallikrein activated by bovine Hageman factor. Takahashi, H., Nagasawa, S., Suzuki, T. J. Biochem. (1980) [Pubmed]
  4. Inhibition of the activation of Hageman factor (factor XII) by human vascular endothelial cell culture supernates. Ratnoff, O.D., Everson, B., Embury, P., Ziats, N.P., Anderson, J.M., Emanuelson, M.M., Malemud, C.J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  5. Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII. Miyazawa, K., Shimomura, T., Kitamura, A., Kondo, J., Morimoto, Y., Kitamura, N. J. Biol. Chem. (1993) [Pubmed]
  6. Mammalian tissue trypsin-like enzymes. Comparative reactivities of human skin tryptase, human lung tryptase, and bovine trypsin with peptide 4-nitroanilide and thioester substrates. Tanaka, T., McRae, B.J., Cho, K., Cook, R., Fraki, J.E., Johnson, D.A., Powers, J.C. J. Biol. Chem. (1983) [Pubmed]
  7. Guinea pig Hageman factor as a vascular permeability enhancement factor. Yamamoto, T., Cochrane, C.G. Am. J. Pathol. (1981) [Pubmed]
  8. Production of prostaglandin D synthase as a keratan sulfate proteoglycan by cultured bovine keratocytes. Berryhill, B.L., Beales, M.P., Hassell, J.R. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  9. Primary structure of bovine Hageman factor (blood coagulation factor XII): comparison with human and guinea pig molecules. Shibuya, Y., Semba, U., Okabe, H., Kambara, T., Yamamoto, T. Biochim. Biophys. Acta (1994) [Pubmed]
  10. Separation of bovine bronchial epithelial cell subpopulations by density centrifugation: a method to isolate ciliated and nonciliated cell fractions. Takizawa, H., Romberger, D., Beckmann, J.D., Matsuda, T., Eccleston-Joyner, C., Shoji, S., Rickard, K.A., Claassen, L.R., Ertl, R.F., Linder, J. Am. J. Respir. Cell Mol. Biol. (1990) [Pubmed]
  11. Serum-free organ culture of suckling rat jejunum: effect of regulatory hormones. Albert, V., Barkla, D., Young, G.P. In Vitro Cell. Dev. Biol. Anim. (1994) [Pubmed]
  12. Conditions for the culture of bovine embryonic myogenic cells. Woods, T.L., Smith, C.W., Zeece, M.G., Jones, S.J. Tissue & cell. (1997) [Pubmed]
  13. Effects of fatty acid regulation on visfatin gene expression in adipocytes. Wen, Y., Wang, H.W., Wu, J., Lu, H.L., Hu, X.F., Cianflone, K. Chin. Med. J. (2006) [Pubmed]
  14. Regulation of the action of hydrocortisone in airway epithelial cells by 11beta-hydroxysteroid dehydrogenase. Feinstein, M.B., Schleimer, R.P. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  15. Influence of culture conditions on the androgen control of secretory component production by acinar cells from the rat lacrimal gland. Hann, L.E., Kelleher, R.S., Sullivan, D.A. Invest. Ophthalmol. Vis. Sci. (1991) [Pubmed]
  16. Spatial and temporal analyses of integrin and Muc-1 expression in porcine uterine epithelium and trophectoderm in vitro. Bowen, J.A., Bazer, F.W., Burghardt, R.C. Biol. Reprod. (1997) [Pubmed]
  17. Leptomeningeal and skin fibroblasts: two different cell types? Colombo, J.A., Napp, M.I., Puissant, V. Int. J. Dev. Neurosci. (1994) [Pubmed]
  18. Stimulatory effect of estrogen on prolactin secretion from primate pituitary cells cultured on extracellular matrix and in serum-free medium. Bethea, C.L. Endocrinology (1984) [Pubmed]
  19. Bovine pinealocytes in monolayer culture: studies on the adrenergic regulation of melatonin secretion. Rüppel, R., Olcese, J. Endocrinology (1991) [Pubmed]
  20. Selective growth in culture of fetal rat renal collecting duct anlagen. Morphologic and biochemical characterization. Perantoni, A., Kan, F.W., Dove, L.F., Reed, C.D. Lab. Invest. (1985) [Pubmed]
  21. Neurons are generated in confluent astroglial cultures of rat neonatal neocortex. Hildebrand, B., Olenik, C., Meyer, D.K. Neuroscience (1997) [Pubmed]
  22. Effects of epidermal growth factor, phorbol ester, and retinoic acid on hormone synthesis and morphology in porcine thyroid follicles cultured in collagen gel. Hishinuma, A., Kasai, K., Ichimura, K., Emoto, T., Shimoda, S. Thyroid (1992) [Pubmed]
  23. Fibronectin and proteoglycan synthesis in long term cultures of cartilage explants in Ham's F12 supplemented with insulin and calcium: effects of the addition of TGF-beta. Burton-Wurster, N., Lust, G. Arch. Biochem. Biophys. (1990) [Pubmed]
  24. Lactating goat mammary gland cells in culture. Hansen, H.O., Knudsen, J. Comparative biochemistry and physiology. A, Comparative physiology. (1991) [Pubmed]
  25. In vitro cartilage regeneration from proliferated adult elastic chondrocytes. Terada, S., Fuchs, J.R., Yoshimoto, H., Fauza, D.O., Vacanti, J.P. Annals of plastic surgery. (2005) [Pubmed]
  26. Organ cultures of embryonic rat tongue support tongue and gustatory papilla morphogenesis in vitro without intact sensory ganglia. Mbiene, J.P., Maccallum, D.K., Mistretta, C.M. J. Comp. Neurol. (1997) [Pubmed]
  27. Collagen substrates for cytogenetic studies of domestic animal embryos. Popescu, C.P., Boscher, J., Cribiu, E.P. J. Hered. (1982) [Pubmed]
  28. Cryopreservation of Osteoblast-Like Cells: Viability and Differentiation with Replacement of Fetal Bovine Serum in vitro. Reuther, T., Kettmann, C., Scheer, M., Kochel, M., Iida, S., Kubler, A.C. Cells Tissues Organs (Print) (2006) [Pubmed]
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