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Gene Review

Afp  -  alpha fetoprotein

Mus musculus

Synonyms: Alpha-1-fetoprotein, Alpha-fetoglobulin, Alpha-fetoprotein, alpha-foetoprotein
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Disease relevance of Afp


Psychiatry related information on Afp

  • Pharmacologic doses of 200 microgram AFP ip three times per week had no effect on either latency period or tumor incidence in mice given injections of MCA and DMBA when compared to albumin-treated and transferrin-treated controls [6].
  • Furthermore, the serum alpha-fetoprotein levels decreased in the combination therapy group, while they increased in the controls [7].
  • Thus, exposure to anti-AFP IgG during the critical period of sexual development in the brain appears to mimic steroidal androgenization of the female mouse [8].

High impact information on Afp

  • One Type III clone produced alpha-fetoprotein and plasminogen activator (visceral endoderm-like), while another clone consisted of trophectodermal cell-like giant cells [9].
  • The cessation of albumin and AFP production is not dependent upon the parental fibroblast nor upon the selection conditions; it is best explained by a shut-off synthesis and could thus reflect the existence of a regulatory mechanism [10].
  • Differential expression of alpha-fetoprotein genes on the inactive X chromosome in extraembryonic and somatic tissues of a transgenic mouse line [11].
  • Tissue-specific activation of a cloned alpha-fetoprotein gene during differentiation of a transfected embryonal carcinoma cell line [12].
  • The differentiation of the transformants to either parietal or visceral endoderm was accompanied by induction of the exogenous template in a manner qualitatively, but not quantitatively, identical to that of the endogenous alpha-fetoprotein gene [12].

Chemical compound and disease context of Afp


Biological context of Afp


Anatomical context of Afp

  • Plasma proteins of the adult type and AFP were localized mainly within the membrane systems of the endoplasmic reticulum and Golgi complex and occasionally on the microvilli [21].
  • In embryos deficient for both genes in the foregut endoderm, no liver bud is evident and expression of the hepatoblast marker alpha-fetoprotein (Afp) is lost [22].
  • Taken together, these results are in agreement with the view that AFP receptors are expressed at the surface of proliferating mouse embryonic fibroblasts and human mammary epithelial cancer cells but absent from the surface of normal human mature cells of the same origin [23].
  • Many of these genes, including the mouse alpha-fetoprotein (AFP) gene, are also expressed in the intestinal epithelium [24].
  • AFP, as transferrin (Tf) used in parallel as a control, are endocytosed through coated pits and vesicles and move then to endosomes in every case; in cells of the late passages, at least a part of the internalized proteins would be routed to lysosomes [23].

Associations of Afp with chemical compounds


Physical interactions of Afp


Regulatory relationships of Afp


Other interactions of Afp

  • The decrease in albumin and AFP mRNAs caused by TGF beta 1 is posttranscriptional and dependent upon de novo RNA and protein synthesis [2].
  • In addition, alpha-fetoprotein and aldolase A mRNA levels were also higher than in normal littermates [33].
  • RESULTS: The mRNA expression of alpha-fetoprotein, albumin (ALB), alpha-1-antitrypsin, and hepatocyte nuclear factor 4alpha was observed earlier in the differentiating cES cells co-cultured with MFLCs, as compared to cES cells undergoing spontaneous differentiation and those subjected to GF-induced differentiation [34].
  • The alpha-fetoprotein (AFP) and H19 genes are transcribed at high levels in the mammalian fetal liver but are rapidly repressed postnatally [1].
  • The alpha-fetoprotein gene (Afp) is a member of a multigenic family that comprises the related genes encoding albumin, alpha-albumin, and vitamin D binding protein [19].

Analytical, diagnostic and therapeutic context of Afp


  1. Hereditary persistence of alpha-fetoprotein and H19 expression in liver of BALB/cJ mice is due to a retrovirus insertion in the Zhx2 gene. Perincheri, S., Dingle, R.W., Peterson, M.L., Spear, B.T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. Posttranscriptional regulation of albumin and alpha-fetoprotein messenger RNA by transforming growth factor-beta 1 requires de novo RNA and protein synthesis. Beauchamp, R.D., Sheng, H.M., Alam, T., Townsend, C.M., Papaconstantinou, J. Mol. Endocrinol. (1992) [Pubmed]
  3. Localization of mouse melanoma growth stimulatory activity gene (Mgsa) between Afp and Gus on chromosome 5 using interspecific backcross mice. Seldin, M.F., Martinez, L., Howard, T.A., Naylor, S.L., Sakaguchi, A.Y. Cytogenet. Cell Genet. (1990) [Pubmed]
  4. Locus unlinked to alpha-fetoprotein under the control of the murine raf and Rif genes. Pachnis, V., Belayew, A., Tilghman, S.M. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  5. alpha-Fetoprotein and other serum proteins synthesized by endodermal sinus tumor transplanted into nude mice. Kaneko, M., Takeuchi, T., Tsuchida, Y., Saito, S., Endo, Y. Gann = Gan. (1980) [Pubmed]
  6. Accelerated plasmacytoma formation in mice treated with alpha-fetoprotein. Gershwin, M.E., Castles, J.J., Makishima, R. J. Natl. Cancer Inst. (1980) [Pubmed]
  7. Eradication of hepatocellular carcinoma xenografts by radiolabelled, lipiodol-inducible gene therapy. Kawashita, Y., Ohtsuru, A., Miki, F., Kuroda, H., Morishita, M., Kaneda, Y., Hatsushiba, K., Kanematsu, T., Yamashita, S. Gene Ther. (2005) [Pubmed]
  8. Characteristics of the androgenization produced in mice by neonatal exposure to alpha-fetoprotein antibodies. Mizejewski, G.J., Vonnegut, M. Teratology (1982) [Pubmed]
  9. Pleiotropic phenotypic expression in cybrids derived from mouse teratocarcinoma cells fused with rat myoblast cytoplasts. Iwakura, Y., Nozaki, M., Asano, M., Yoshida, M.C., Tsukada, Y., Hibi, N., Ochiai, A., Tahara, E., Tosu, M., Sekiguchi, T. Cell (1985) [Pubmed]
  10. The control of serum protein synthesis in hepatoma-fibroblast hybrids. Szpirer, J., Szpirer, C. Cell (1975) [Pubmed]
  11. Differential expression of alpha-fetoprotein genes on the inactive X chromosome in extraembryonic and somatic tissues of a transgenic mouse line. Krumlauf, R., Chapman, V.M., Hammer, R.E., Brinster, R., Tilghman, S.M. Nature (1986) [Pubmed]
  12. Tissue-specific activation of a cloned alpha-fetoprotein gene during differentiation of a transfected embryonal carcinoma cell line. Scott, R.W., Vogt, T.F., Croke, M.E., Tilghman, S.M. Nature (1984) [Pubmed]
  13. The thyroid hormone down-regulates the mouse alpha-foetoprotein promoter. Caturla, M., Van Reeth, T., Drèze, P., Szpirer, J., Szpirer, C. Mol. Cell. Endocrinol. (1997) [Pubmed]
  14. Genetic analysis of L-ethionine-mediated induction of alpha-fetoprotein in mice. Mifflin, R.C., Moller, P.C., Papaconstantinou, J. Somat. Cell Mol. Genet. (1988) [Pubmed]
  15. A peptide derived from alpha-fetoprotein prevents the growth of estrogen-dependent human breast cancers sensitive and resistant to tamoxifen. Bennett, J.A., Mesfin, F.B., Andersen, T.T., Gierthy, J.F., Jacobson, H.I. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  16. Inhibition of estrogen-dependent breast cancer growth by a reaction product of alpha-fetoprotein and estradiol. Jacobson, H.I., Bennett, J.A., Mizejewski, G.J. Cancer Res. (1990) [Pubmed]
  17. Therapeutic effect of treatment with polyclonal or monoclonal antibodies to alpha-fetoprotein that have been conjugated to daunomycin via a dextran bridge: studies with an alpha-fetoprotein-producing rat hepatoma tumor model. Tsukada, Y., Ohkawa, K., Hibi, N. Cancer Res. (1987) [Pubmed]
  18. alpha-Fetoprotein gene sequences mediating Afr2 regulation during liver regeneration. Jin, D.K., Vacher, J., Feuerman, M.H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  19. Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility. Gabant, P., Forrester, L., Nichols, J., Van Reeth, T., De Mees, C., Pajack, B., Watt, A., Smitz, J., Alexandre, H., Szpirer, C., Szpirer, J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  20. Mouse alpha-fetoprotein gene 5' regulatory elements are required for postnatal regulation by raf and Rif. Spear, B.T. Mol. Cell. Biol. (1994) [Pubmed]
  21. Human yolk sac tumor serially transplanted in nude mice: its morphologic and functional properties. Hata, J.I., Ueyama, Y., Tamaoki, N., Akatsuka, A., Yoshimura, S., Shimuzu, K., Morikawa, Y., Furukawa, T. Cancer (1980) [Pubmed]
  22. The initiation of liver development is dependent on Foxa transcription factors. Lee, C.S., Friedman, J.R., Fulmer, J.T., Kaestner, K.H. Nature (2005) [Pubmed]
  23. A study, by electron microscopy, of the specific uptake of alpha-fetoprotein by mouse embryonic fibroblasts in relation to in vitro aging, and by human mammary epithelial tumour cells in comparison with normal donors' cells. Geuskens, M., Dupressoir, T., Uriel, J. J. Submicrosc. Cytol. Pathol. (1991) [Pubmed]
  24. HNF-1 alpha and HNF-1 beta expression in mouse intestinal crypts. Serfas, M.S., Tyner, A.L. Am. J. Physiol. (1993) [Pubmed]
  25. Establishment and partial characterization of SV40 virus-immortalized hepatocyte lines of normal and lethal mutant mice carrying a deletion on chromosome 7. Paul, D., Kwon, B.S., Höhne, M., Tönjes, R., Haq, A.K., Hoffmann, B. J. Cell. Physiol. (1989) [Pubmed]
  26. Genetic analysis of alpha-fetoprotein synthesis in mice. Belayew, A., Tilghman, S.M. Mol. Cell. Biol. (1982) [Pubmed]
  27. Glucocorticoid stimulates primate but inhibits rodent alpha-fetoprotein gene promoter. Nakabayashi, H., Koyama, Y., Sakai, M., Li, H.M., Wong, N.C., Nishi, S. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  28. A transforming growth factor beta 2 (TGF-beta 2)-like immunosuppressive factor in amniotic fluid and localization of TGF-beta 2 mRNA in the pregnant uterus. Altman, D.J., Schneider, S.L., Thompson, D.A., Cheng, H.L., Tomasi, T.B. J. Exp. Med. (1990) [Pubmed]
  29. Identification of nonhistone chromosomal proteins binding specifically to cloned alpha-fetoprotein DNA sequences. Lesser, B.H., Chan, H.W., Stockton, J.F. Can. J. Biochem. Cell Biol. (1983) [Pubmed]
  30. Regulation of alpha-fetoprotein by nuclear factor-kappaB protects hepatocytes from tumor necrosis factor-alpha cytotoxicity during fetal liver development and hepatic oncogenesis. Cavin, L.G., Venkatraman, M., Factor, V.M., Kaur, S., Schroeder, I., Mercurio, F., Beg, A.A., Thorgeirsson, S.S., Arsura, M. Cancer Res. (2004) [Pubmed]
  31. Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action. De Mees, C., Laes, J.F., Bakker, J., Smitz, J., Hennuy, B., Van Vooren, P., Gabant, P., Szpirer, J., Szpirer, C. Mol. Cell. Biol. (2006) [Pubmed]
  32. The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells. Li, M.S., Li, P.F., Yang, F.Y., He, S.P., Du, G.G., Li, G. Cell Res. (2002) [Pubmed]
  33. Proto-oncogene c-jun and c-fos messenger RNAs increase in the liver of carnitine-deficient juvenile visceral steatosis (jvs) mice. Tomomura, M., Nakagawa, K., Saheki, T. FEBS Lett. (1992) [Pubmed]
  34. Promoted differentiation of cynomolgus monkey ES cells into hepatocyte-like cells by co-culture with mouse fetal liver-derived cells. Saito, K., Yoshikawa, M., Ouji, Y., Moriya, K., Nishiofuku, M., Ueda, S., Hayashi, N., Ishizaka, S., Fukui, H. World J. Gastroenterol. (2006) [Pubmed]
  35. E-cadherin synergistically induces hepatospecific phenotype and maturation of embryonic stem cells in conjunction with hepatotrophic factors. Dasgupta, A., Hughey, R., Lancin, P., Larue, L., Moghe, P.V. Biotechnol. Bioeng. (2005) [Pubmed]
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