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Gene Review

AFP  -  alpha-fetoprotein

Homo sapiens

Synonyms: AFPD, Alpha-1-fetoprotein, Alpha-fetoglobulin, Alpha-fetoprotein, FETA, ...
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Disease relevance of AFP

  • Intratumoral injection of AdV resulted in growth retardation and regression in a majority of established hepatomas, but with a much wider therapeutic index and less systemic toxicity using the AFP vector [1].
  • Therefore, both TSG3 and TSG17 tumors were regarded as non-hepatoid, poorly differentiated adenocarcinomas which could be differentiated from any types of AFP-producing gastric carcinoma [2].
  • At univariate analysis, high AFP (p < 0.0001), HBsAg positivity (p=0.05), p53 mutation (p=0.0004), liver cirrhosis (p=0.0094), large tumor (p=0.0003), vascular invasion (p < 0.0001) and early recurrence (p < 0.0001) were significant unfavorable prognostic factors [3].
  • Our data show that some non-hepatoid AFP-producing gastric carcinomas have lower liver-metastasizing potential than hepatoid AFP-producing gastric carcinomas [2].
  • Gastric cancers producing alpha-fetoprotein (AFP) have a poor prognosis and a high incidence of liver metastasis [4].

Psychiatry related information on AFP


High impact information on AFP


Chemical compound and disease context of AFP


Biological context of AFP

  • This mechanism for p53-mediated repression of AFP gene expression may be active during hepatic differentiation and lost in the process of tumorigenesis [19].
  • Immunohistochemical studies revealed that the AFP-binding protein(s) is expressed in blood vessels of chorionic villi from placentae of the second and the third but not of the first trimester during pregnancy [20].
  • The GC gene, and the tandemly linked ALB and AFP genes, have been previously localized to human chromosome 4q11-13 [21].
  • CONCLUSIONS: These results suggest that AFP-producing gastric cancers have high malignant potential (high proliferative activity, weak apoptosis, and rich neovascularization) compared with that of AFP-negative gastric cancers [14].
  • While the primitive lamphrey possesses a serum protein twice the size of mammalian albumin, the bony fishes, reptiles, and amphibians display two ALB-like molecules sharing amino acid sequence similarity to mammalian AFP [22].

Anatomical context of AFP


Associations of AFP with chemical compounds

  • Induction of p53 in response to actinomycin D or hypoxic stress decreases AFP expression [19].
  • Like the founding family member p53, TA-p73 represses AFP expression by chromatin structure alteration, targeting reduction of acetylated histone H3 lysine 9 and increased dimethylated histone H3 lysine 9 levels [25].
  • Alpha-fetoprotein (AFP) is a 65-kDa oncofetal glycoprotein found in fetal and maternal fluids during pregnancy [26].
  • Here we comparatively analyze, in PBMCs from patients with AIDS and related syndromes, (1) changes in membrane fluidity, measured as the cholesterol/phospholipid ratio (CH/PL), and (2) changes in the expression of AFP receptors and of the alpha chain of IL-2 receptor (TAC antigen) [27].
  • In an immunohistochemical analysis of 13 SpHCC tumors, cytokeratin CAM 5.2 and AFP were positive in 8 (62%) tumors and 3 (23%) tumors in both ordinary HCC and spindle cell components, respectively [28].
  • Overall, downstaging HCC patients with high AFP is feasible and leads to similar intent-to-treat and post-transplant survivals to those of patients with AFP persistently low [29].
  • Assessment of AFP response may be considered as an alternative to RECIST to capture sorafenib activity in HCC [30].

Physical interactions of AFP

  • The present results provide strong evidence that AFP directly binds to CCR5 expressed by human primary macrophages and by transfected CCR5+ HeLa cells [31].
  • We have isolated a full-length cDNA encoding a protein (ATBF1) that binds to an AT-rich motif in the human alpha-fetoprotein gene enhancer [32].
  • Addition of the 2-F diminishes ER and AFP-binding affinities while augmenting the affinity for the SHBG [33].
  • This strongly suggests that competition between NF-1 and HNF-1 for binding to their overlapping binding sites on the AFP promoter is critical for modulating its activity [34].
  • Using solid-phase, chromatin-assembled AFP DNA templates and analysis of chromatin structure and transcription in vitro, we find that p53 binds DNA and alters chromatin structure at the AFP core promoter to regulate transcription [35].

Co-localisations of AFP


Regulatory relationships of AFP

  • Western blot assay also demonstrated that AFP promoted the expression of mutative p53 and p21(ras) proteins, and the increased rate of those proteins was 13.0%, 39.9%, and 70.9%, as well as 35.2%, 102.6%, and 46.8% at 6, 12, and 24 h, respectively, as compared with the control [37].
  • Treatment with MMC of AFP-gastric cancer cells enhanced their susceptibility to LAK-T cells and induced ATBF1 gene expression [38].
  • These results indicate that the ability of extracellular matrix materials to enhance attachment and/or growth is different from that to enhance AFP and albumin production in HuH-6 and probably in HuH-7 [39].
  • The targeted expression of the human interleukin-2/interferon alpha2b fused gene in alpha-fetoprotein-expressing hepatocellular carcinoma cells [40].
  • Alpha-fetoprotein positively regulates cytochrome c-mediated caspase activation and apoptosome complex formation [41].
  • This represents the first direct evidence that ZHX2 represses AFP [42].

Other interactions of AFP

  • Interestingly, in most cases, there was no correlation between GPC3 and AFP values [43].
  • These findings provide novel evidence that p33(ING1b) represses AFP transcription by at least two mechanisms, one of which includes p53 [23].
  • Although individual family members display an approximate clock-like evolution, there are significant deviations-the rates of divergence for AFP differ by a factor of 7, the rates for ALB differ by a factor of 2 [44].
  • When combined with EGF, however, AFP dose-dependently increased proliferation to levels equal to that obtained with 10% FCS (2.3-fold increase vs PDS/LDL controls) [24].
  • The characteristics, including metastatic potential, of 5 xenografts of alpha-fetoprotein (AFP)-producing gastric carcinomas in nude mice, designated TSG1, TSG3, TSG11, TSG17 and TSG20, were examined [2].

Analytical, diagnostic and therapeutic context of AFP

  • Western blot analysis of proteins present in developmentally staged, liver nuclear extracts reveal a one-to-one correlation between activation of p53 protein and repression of AFP during hepatic development [19].
  • This study was to elucidate the significance and related factors of AFP elevation in HCC in 781 unifocal HCCs receiving curative hepatectomy [3].
  • Although the determination of AFP levels in maternal blood and amniotic fluid is widely used in the prenatal diagnosis of NTDs, demonstration of AFP in amniotic fluid cells by means of immunocytochemistry has not been described [45].
  • The phylogeny of the AFP molecule should prove useful for investigators seeking markers for animal models of human diseases, serological cross-reactivity between AFP molecular species, identification of larval or fetal protein homologs of AFP, and provide strategies for biochemical purification and physiological studies [22].
  • The rats were killed at different time points after the treatment and the liver tissue was histopathologically studied and human AFP and ALB detected by immunohistochemistry [46].


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  2. Different characteristics of hepatoid and non-hepatoid alpha-fetoprotein-producing gastric carcinomas: an experimental study using xenografted tumors. Aizawa, K., Motoyama, T., Suzuki, S., Tanaka, N., Yabusaki, H., Tanaka, S., Muto, I., Tanaka, O., Hatakeyama, K. Int. J. Cancer (1994) [Pubmed]
  3. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Peng, S.Y., Chen, W.J., Lai, P.L., Jeng, Y.M., Sheu, J.C., Hsu, H.C. Int. J. Cancer (2004) [Pubmed]
  4. High frequency of c-Met expression in gastric cancers producing alpha- fetoprotein. Amemiya, H., Kono, K., Mori, Y., Takahashi, A., Ichihara, F., Iizuka, H., Sekikawa, T., Matsumoto, Y. Oncology (2000) [Pubmed]
  5. Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. Le Ber, I., Bouslam, N., Rivaud-Péchoux, S., Guimarães, J., Benomar, A., Chamayou, C., Goizet, C., Moreira, M.C., Klur, S., Yahyaoui, M., Agid, Y., Koenig, M., Stevanin, G., Brice, A., Dürr, A. Brain (2004) [Pubmed]
  6. Diagnosis of premature rupture of membranes with an improved alpha-fetoprotein monoclonal antibody kit. Kishida, T., Hirao, A., Matsuura, T., Katamine, T., Yamada, H., Sagawa, T., Fujimoto, S. Clin. Chem. (1995) [Pubmed]
  7. Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C. Bayati, N., Silverman, A.L., Gordon, S.C. Am. J. Gastroenterol. (1998) [Pubmed]
  8. A multidirectional sonographic approach to elevated amniotic alpha-fetoprotein or positive acetylcholinesterase. Blumenfeld, Z., Zimmer, E., Bronshtein, M. Obstetrics and gynecology. (1995) [Pubmed]
  9. Alpha fetoprotein screening and diagnosis of fetal open neural tube defects: the need for quality control. Wald, N.J., Cuckle, H.S., Catz, C., Dayton, D., Reimer, C.B. Am. J. Obstet. Gynecol. (1981) [Pubmed]
  10. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Moreira, M.C., Klur, S., Watanabe, M., Németh, A.H., Le Ber, I., Moniz, J.C., Tranchant, C., Aubourg, P., Tazir, M., Schöls, L., Pandolfo, M., Schulz, J.B., Pouget, J., Calvas, P., Shizuka-Ikeda, M., Shoji, M., Tanaka, M., Izatt, L., Shaw, C.E., M'Zahem, A., Dunne, E., Bomont, P., Benhassine, T., Bouslam, N., Stevanin, G., Brice, A., Guimarães, J., Mendonça, P., Barbot, C., Coutinho, P., Sequeiros, J., Dürr, A., Warter, J.M., Koenig, M. Nat. Genet. (2004) [Pubmed]
  11. Integrated screening for Down's syndrome on the basis of tests performed during the first and second trimesters. Wald, N.J., Watt, H.C., Hackshaw, A.K. N. Engl. J. Med. (1999) [Pubmed]
  12. Increased nuchal translucency as a marker for fetal chromosomal defects. Taipale, P., Hiilesmaa, V., Salonen, R., Ylöstalo, P. N. Engl. J. Med. (1997) [Pubmed]
  13. Dimeric inhibin A as a marker for Down's syndrome in early pregnancy. Aitken, D.A., Wallace, E.M., Crossley, J.A., Swanston, I.A., van Pareren, Y., van Maarle, M., Groome, N.P., Macri, J.N., Connor, J.M. N. Engl. J. Med. (1996) [Pubmed]
  14. Alpha-fetoprotein-producing gastric cancer: histochemical analysis of cell proliferation, apoptosis, and angiogenesis. Koide, N., Nishio, A., Igarashi, J., Kajikawa, S., Adachi, W., Amano, J. Am. J. Gastroenterol. (1999) [Pubmed]
  15. Prevention of N-methyl-N-nitrosourea-induced breast cancer by alpha-fetoprotein (AFP)-derived peptide, a peptide derived from the active site of AFP. Parikh, R.R., Gildener-Leapman, N., Narendran, A., Lin, H.Y., Lemanski, N., Bennett, J.A., Jacobson, H.I., Andersen, T.T. Clin. Cancer Res. (2005) [Pubmed]
  16. The enzymatic basis for the conversion of nonfucosylated to fucosylated alpha-fetoprotein by acyclic retinoid treatment in human hepatoma cells: activation of alpha1-6 fucosyltransferase. Noda, K., Miyoshi, E., Kitada, T., Nakahara, S., Gao, C.X., Honke, K., Shiratori, Y., Moriwaki, H., Sasaki, Y., Kasahara, A., Hori, M., Hayashi, N., Taniguchi, N. Tumour Biol. (2002) [Pubmed]
  17. Immunohistochemical expression of pi class glutathione S-transferase and alpha-fetoprotein in hepatocellular carcinoma and chronic liver disease. Yusof, Y.A., Yan, K.L., Hussain, S.N. Anal. Quant. Cytol. Histol. (2003) [Pubmed]
  18. Epithelial layer formation in differentiating aggregates of F9 embryonal carcinoma cells. Grover, A., Oshima, R.G., Adamson, E.D. J. Cell Biol. (1983) [Pubmed]
  19. p53-mediated repression of alpha-fetoprotein gene expression by specific DNA binding. Lee, K.C., Crowe, A.J., Barton, M.C. Mol. Cell. Biol. (1999) [Pubmed]
  20. Oncodevelopmental alpha-fetoprotein acts as a selective proangiogenic factor on endothelial cell from the fetomaternal unit. Liang, O.D., Korff, T., Eckhardt, J., Rifaat, J., Baal, N., Herr, F., Preissner, K.T., Zygmunt, M. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  21. Tandem arrangement of the human serum albumin multigene family in the sub-centromeric region of 4q: evolution and chromosomal direction of transcription. Nishio, H., Heiskanen, M., Palotie, A., Bélanger, L., Dugaiczyk, A. J. Mol. Biol. (1996) [Pubmed]
  22. The phylogeny of alpha-fetoprotein in vertebrates: survey of biochemical and physiological data. Mizejewski, G.J. Crit. Rev. Eukaryot. Gene Expr. (1995) [Pubmed]
  23. ING1 represses transcription by direct DNA binding and through effects on p53. Kataoka, H., Bonnefin, P., Vieyra, D., Feng, X., Hara, Y., Miura, Y., Joh, T., Nakabayashi, H., Vaziri, H., Harris, C.C., Riabowol, K. Cancer Res. (2003) [Pubmed]
  24. Human alpha fetoprotein enhances epidermal growth factor proliferative activity upon porcine granulosa cells in monolayer culture. Leal, J.A., May, J.V., Keel, B.A. Endocrinology (1990) [Pubmed]
  25. Family members p53 and p73 act together in chromatin modification and direct repression of alpha-fetoprotein transcription. Cui, R., Nguyen, T.T., Taube, J.H., Stratton, S.A., Feuerman, M.H., Barton, M.C. J. Biol. Chem. (2005) [Pubmed]
  26. Amelioration of autoimmune neuroinflammation by recombinant human alpha-fetoprotein. Irony-Tur-Sinai, M., Grigoriadis, N., Lourbopoulos, A., Pinto-Maaravi, F., Abramsky, O., Brenner, T. Exp. Neurol. (2006) [Pubmed]
  27. Expression of alpha-fetoprotein and interleukin 2 receptors and impairment of membrane fluidity in peripheral blood mononuclear cells from AIDS and related syndromes. Macho, A., Aguilar, J.J., Naval, J., Girard, P.M., Uriel, J. AIDS Res. Hum. Retroviruses (1994) [Pubmed]
  28. Spindle cell hepatocellular carcinoma. A clinicopathologic and immunohistochemical analysis of 15 cases. Maeda, T., Adachi, E., Kajiyama, K., Takenaka, K., Sugimachi, K., Tsuneyoshi, M. Cancer (1996) [Pubmed]
  29. The impact of waiting list alpha-fetoprotein changes on the outcome of liver transplant for hepatocellular carcinoma. Merani, S., Majno, P., Kneteman, N.M., Berney, T., Morel, P., Mentha, G., Toso, C. J. Hepatol. (2011) [Pubmed]
  30. Usefulness of alpha-fetoprotein response in patients treated with sorafenib for advanced hepatocellular carcinoma. Personeni, N., Bozzarelli, S., Pressiani, T., Rimassa, L., Tronconi, M.C., Sclafani, F., Carnaghi, C., Pedicini, V., Giordano, L., Santoro, A. J. Hepatol. (2012) [Pubmed]
  31. Human alpha-fetoprotein binds to primary macrophages. Atemezem, A., Mbemba, E., Marfaing, R., Vaysse, J., Pontet, M., Saffar, L., Charnaux, N., Gattegno, L. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  32. A human alpha-fetoprotein enhancer-binding protein, ATBF1, contains four homeodomains and seventeen zinc fingers. Morinaga, T., Yasuda, H., Hashimoto, T., Higashio, K., Tamaoki, T. Mol. Cell. Biol. (1991) [Pubmed]
  33. 18F-labeled difluoroestradiols: preparation and preclinical evaluation as estrogen receptor-binding radiopharmaceuticals. Seimbille, Y., Rousseau, J., Bénard, F., Morin, C., Ali, H., Avvakumov, G., Hammond, G.L., van Lier, J.E. Steroids (2002) [Pubmed]
  34. Members of the CAAT/enhancer-binding protein, hepatocyte nuclear factor-1 and nuclear factor-1 families can differentially modulate the activities of the rat alpha-fetoprotein promoter and enhancer. Bois-Joyeux, B., Danan, J.L. Biochem. J. (1994) [Pubmed]
  35. p53 targets chromatin structure alteration to repress alpha-fetoprotein gene expression. Ogden, S.K., Lee, K.C., Wernke-Dollries, K., Stratton, S.A., Aronow, B., Barton, M.C. J. Biol. Chem. (2001) [Pubmed]
  36. Detection and measurement of alpha-fetoprotein in human breast cancer cytosol after treatment with 0.4 M potassium chloride. Sarcione, E.J., Zloty, M., Delluomo, D.S., Mizejewski, G., Jacobson, H. Cancer Res. (1983) [Pubmed]
  37. Alpha-fetoprotein stimulated the expression of some oncogenes in human hepatocellular carcinoma Bel 7402 cells. Li, M.S., Li, P.F., Chen, Q., Du, G.G., Li, G. World J. Gastroenterol. (2004) [Pubmed]
  38. Susceptibility to killer T cells of gastric cancer cells enhanced by Mitomycin-C involves induction of ATBF1 and activation of p21 (Waf1/Cip1) promoter. Miura, Y., Kataoka, H., Joh, T., Tada, T., Asai, K., Nakanishi, M., Okada, N., Okada, H. Microbiol. Immunol. (2004) [Pubmed]
  39. Effects of various substrates on human hepatoblastoma and hepatoma cell culture. Tokiwa, T., Miyagiwa, M., Kusaka, Y., Muraoka, A., Sato, J. Cell Biol. Int. Rep. (1988) [Pubmed]
  40. The targeted expression of the human interleukin-2/interferon alpha2b fused gene in alpha-fetoprotein-expressing hepatocellular carcinoma cells. He, P., Tang, Z.Y., Liu, B.B., Ye, S.L., Liu, Y.K. J. Cancer Res. Clin. Oncol. (1999) [Pubmed]
  41. Alpha-fetoprotein positively regulates cytochrome c-mediated caspase activation and apoptosome complex formation. Semenkova, L., Dudich, E., Dudich, I., Tokhtamisheva, N., Tatulov, E., Okruzhnov, Y., Garcia-Foncillas, J., Palop-Cubillo, J.A., Korpela, T. Eur. J. Biochem. (2003) [Pubmed]
  42. ZHX2 is a repressor of alpha-fetoprotein expression in human hepatoma cell lines. Shen, H., Luan, F., Liu, H., Gao, L., Liang, X., Zhang, L., Sun, W., Ma, C. J. Cell. Mol. Med. (2008) [Pubmed]
  43. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Capurro, M., Wanless, I.R., Sherman, M., Deboer, G., Shi, W., Miyoshi, E., Filmus, J. Gastroenterology (2003) [Pubmed]
  44. The molecular clock runs at different rates among closely related members of a gene family. Gibbs, P.E., Witke, W.F., Dugaiczyk, A. J. Mol. Evol. (1998) [Pubmed]
  45. Immunocytochemical characterization of amniotic fluid macrophages in cases of fetal neural tube defects. Polgar, K., Abel, G., Laczko, J., Sipka, S., Papp, Z. Am. J. Clin. Pathol. (1987) [Pubmed]
  46. Differentiation of human umbilical cord blood stem cells into hepatocytes in vivo and in vitro. Tang, X.P., Zhang, M., Yang, X., Chen, L.M., Zeng, Y. World J. Gastroenterol. (2006) [Pubmed]
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