Disease relevance of Afp

• Hereditary persistence of alpha-fetoprotein and H19 expression in liver of BALB/cJ mice is due to a retrovirus insertion in the Zhx2 gene [1].
• We have examined TGF beta 1 regulation of albumin and alpha-fetoprotein (AFP) mRNA levels in a well differentiated mouse hepatoma cell line (BWTG3) [2].
• Localization of mouse melanoma growth stimulatory activity gene (Mgsa) between Afp and Gus on chromosome 5 using interspecific backcross mice [3].
• The repression of H19 mRNA in neonatal liver occurs several days after the decrease in alpha-fetoprotein mRNA, whereas inductions of both mRNAs during the differentiation of F9 teratocarcinoma cells into visceral endoderm were identical [4].
• alpha-Fetoprotein and other serum proteins synthesized by endodermal sinus tumor transplanted into nude mice [5].

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

• The thyroid hormone (T3) was shown to down regulate the level of alpha-foetoprotein (AFP) mRNA in hepatoma cells HepG2 [13].
• A single intraperitoneal injection of L-ethionine (0.5 mg/g body weight) resulted in significant triglyceride accumulation in hepatic parenchymal cells and increased AFP synthesis 48-96 h following injection [14].
• An 8-mer peptide (EMTOVNOG) derived from alpha-fetoprotein was compared with tamoxifen for activity against growth of human breast cancer xenografts implanted in immune-deficient mice [15].
• We describe herein the effect of rodent AFP/E2 on the in vivo growth of two estrogen-dependent breast cancers, the MCF-7 human breast cancer and the MTW9A rat mammary cancer [16].
• 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 [17].

Biological context of Afp

• The genetic regulation of the basal level of AFP gene expression in adult liver by the Afr1 gene was undisturbed [18].
• alpha-Fetoprotein gene sequences mediating Afr2 regulation during liver regeneration [18].
• We show that this transgene was subject to characteristic AFP tissue-specific and developmental regulation, in that it was highly expressed in the yolk sac and the fetal liver and gut but not in normal adult tissues [18].
• Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility [19].
• A fragment of the AFP 5' region containing enhancer element I, the repressor, and the promoter was linked to the mouse class I H-2Dd structural gene [20].

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

• Pretreatment with actinomycin-D prevented the TGF beta 1-induced decrease in albumin and AFP mRNA levels [2].
• Cycloheximide pretreatment blocked the TGF beta 1-induced decrease in albumin and AFP mRNA levels [2].
• Both lines synthesized arginine and contained albumin and alpha-fetoprotein (AFP) mRNAs [25].
• Liver AFP mRNA concentrations during normal development and after carbon tetrachloride administration were measured and shown to correlate exactly with the serum protein concentrations [26].
• Like human, activity of the AFP promoter from other primates was stimulated by the synthetic glucocorticoid dexamethasone (Dex) in various cell lines [27].

Physical interactions of Afp

• This active and anti-TGF-beta 2-neutralizable factor chromatographs at approximately 70 kD on Sephadex at neutral pH and appears to be able to complex with alpha-fetoprotein in native amniotic fluid [28].
• Identification of nonhistone chromosomal proteins binding specifically to cloned alpha-fetoprotein DNA sequences [29].

Regulatory relationships of Afp

• Locus unlinked to alpha-fetoprotein under the control of the murine raf and Rif genes [4].
• The mouse alpha-fetoprotein (AFP) gene is expressed at high levels in the yolk sac and fetal liver and at low levels in the fetal gut [20].
• We show that repression of IKK-2 activity in hepatocellular carcinomas promotes down-regulation of AFP gene expression [30].
• Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action [31].
• In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L [32].

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

• Also, if cells were treated with actinomycin-D after a 12-h exposure to TGF beta 1, actinomycin-D abrogated the further decrease in albumin and AFP mRNA levels that occurred after treatment with TGF beta 1 alone [2].
• Reverse-transcriptase polymerase chain reaction was used to delineate the most differentiating condition in terms of early (alpha-fetoprotein (AFP)), mid (albumin), and late-hepatic (glucose-6-phosphatase) markers in relation to growth factor presentation for both CE-ES and CD-ES cells [35].
• The intracellular localization of AFP, alpha AT, Tf, and Alb was also investigated by immunoelectron microscopy [21].
• 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 [23].
• By performing a series of genetic crosses, we identified two unlinked genetic loci that acted independently to affect the inducibility of AFP mRNA [26].

References