Disease relevance of Afp

• Loss of specific sets of DNase I-hypersensitive sites accompanies the cessation of transcription for the Afp gene in adult rat liver and in a "dedifferentiated" hepatoma cell line [1].
• Immunofluorescent localization of alpha fetoprotein in yolk sac carcinomas of the rat [2].
• These hemangiosarcomas were readily transplantable and did not produce alpha-fetoprotein [3].
• Cellular alpha-fetoprotein was found by immunoperoxidase staining in portions of hepatocellular carcinomas, but not in foci, adenomas, and nonneoplastic areas [4].
• Replication-defective, amphotrophic retroviruses were constructed containing a chimeric varicella-zoster virus thymidine kinase (VZV TK) gene that is transcriptionally regulated by either the hepatoma-associated alpha-fetoprotein or liver-associated albumin transcriptional regulatory sequences [5].

High impact information on Afp

• This pattern of expression mirrors the complex pattern of expression of many genes, such as alpha-fetoprotein, alpha 1-antitrypsin, and fibrinogen, whose promoters contain HNF-1 sites [6].
• The conjugates (DM:PLGA:immunoglobulin molar ratio, 19.6:2.8:1 or 11.8:1.1:1) were more potent than DM in in vitro cytotoxicity against the AFP-producing rat ascites hepatoma cell line AH66 [7].
• An anti-alpha-fetoprotein antibody-daunorubicin conjugate with a novel poly-L-glutamic acid derivative as intermediate drug carrier [7].
• In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunorubicin [(DM) daunomycin] was conjugated with an affinity-purified horse antibody to rat alpha-fetoprotein (AFP) with a novel derivative of poly-L-glutamic acid (PLGA) as the intermediate drug carrier [7].
• Age-dependent growth inhibition of estrogen-sensitive rat mammary tumors. Probable role of alpha-fetoprotein [8].

Chemical compound and disease context of Afp

• Growth inhibition of estrogen-sensitive rat mammary tumors. Effect of an alpha-fetoprotein-secreting hepatoma [9].
• Stable transfection assays were more sensitive and accurate than transient expression assays in a Morris 7777 rat hepatoma recipient (Hepa7.6), selected for its strong AFP repression by dexamethasone [10].
• alpha-Fetoprotein-mediated transfer of arachidonic acid into cultured cloned cells derived from a rat rhabdomyosarcoma [11].
• Cis-acting elements involved in the control of rat alpha-fetoprotein gene expression in the liver and its modulation by glucocorticoid hormones were detected after transfection of chloramphenicol acetyltransferase constructs and their transient expression into two hepatoma cell lines [12].
• Tunicamycin did not affect the synthesis or secretion of AFP by hepatoma cells [13].

Biological context of Afp

• The resultant nucleotide sequence of alpha-fetoprotein was exhaustively compared to the nucleotide sequence of the mRNA encoding rat serum albumin [14].
• The amino acid sequence of rat alpha-fetoprotein has been deduced from the nucleotide sequence, and its comparison to rat serum albumin's amino acid sequence reveals a 34% homology [14].
• Sequence homology between RNAs encoding rat alpha-fetoprotein and rat serum albumin [14].
• The rat alpha-fetoprotein and albumin genes. Transcriptional control and comparison of the sequence organization and promoter region [15].
• The rat alpha-fetoprotein ( afp ) gene is controlled by three enhancers whose function depends on their interaction with liver-enriched transcription factors [16].

Anatomical context of Afp

• The rat adult liver and hepatocyte lines express an 1.7-kb variant alpha-fetoprotein (AFP) mRNA which differs from the 2.2-kb fetal AFP transcript in sequence in the 5' region [17].
• Similarly, in Afp-producing rat tissues and cell lines we mapped one DNase I-hypersensitive region close to the promoter region and two cleavage sites further upstream at approximately 2.2 and approximately 3.8 kb from the cap site [1].
• Alpha-fetoprotein: the major high-affinity estrogen binder in rat uterine cytosols [18].
• alpha-Fetoprotein is not a component of the estradiol receptor of the rat uterus [19].
• We have examined the DNase I sensitivity of the albumin and alpha-fetoprotein (AFP) genes in different rat tissues (adult liver and kidney) and cloned cell lines (hepatoma 7777-C8, JF1 fibroblasts), which show drastic differences in the level of expression of these two genes [20].

Associations of Afp with chemical compounds

• Hepatocyte nuclear factor-6 stimulates transcription of the alpha-fetoprotein gene and synergizes with the retinoic-acid-receptor-related orphan receptor alpha-4 [16].
• On the mechanism of bile acid inhibition of rat sterol 12alpha-hydroxylase gene (CYP8B1) transcription: roles of alpha-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha [21].
• The results strongly suggested that a) the malignant properties of E2-sensitive cells in adult hosts can be controlled by AFP, and b) the mechanism by which AFP inhibits the growth of E2-sensitive cells is independent of the E2 "trapping" phenomenon [9].
• Pulse and pulse-chase experiments demonstrated that dexamethasone inhibited the synthesis of AFP but not its secretion [22].
• Radioimmunoassay of media from cell cultures grown in the presence of glucocorticoid (dexamethasone or cortisol) showed a reduction in AFP, an increase in albumin, and no significant change in transferrin accumulation, as compared to controls [22].

Physical interactions of Afp

• It has been recently reported that bile acid-activated farnesoid X receptor (FXR) induces the small heterodimer partner (SHP) that interacts with alpha-fetoprotein transcription factor (FTF) and down-regulates CYP7A1 transcription [21].

Regulatory relationships of Afp

• Cellular analysis of the kinetics of alpha-fetoprotein and nuclear oncogene activation in primary cultures of adult rat hepatocytes stimulated by epidermal growth factor [23].

Other interactions of Afp

• RESULTS: Under the specified culture conditions, rat MSCs co-cultured with FLC expressed albumin, CK-18, and AFP-RNA over two weeks [24].
• The effect of transforming growth factor beta (TGF-beta) on morphology, actin cytoskeleton organization, anchorage-dependent proliferation, anchorage-independent proliferation, and alpha-fetoprotein secretion in a series of related hepatocyte-derived cell lines was measured [25].
• Albumin-specific transcripts were decreased in all hepatocellular carcinoma but there was no consistent coordinated increase in alpha-fetoprotein-specific transcripts. c-myc and raf transcripts increased at the very early preneoplastic foci stage and continued to increase throughout the neoplastic process [26].
• Also, the differentiation of oval cells into hepatocytes coincided with the loss of alpha-fetoprotein and OV-6 staining, and the replacement of the biliary cell-specific alpha6 integrin and connexin 43 with the hepatocyte-specific alpha1 integrin and connexin 32 [27].
• The serum vitamin D-binding protein (DBP), a member of a multigene family that includes alpha-fetoprotein (alpha FP) and albumin (ALB), is expressed at high levels in the adult liver [28].

Analytical, diagnostic and therapeutic context of Afp

• Alpha fetoprotein (AFP) was detected in the sera by immunoprecipitation [29].
• This inhibitory effect of AFP could not be attributed to a "functional castration" resulting from the trapping of 17 beta-estradiol (E2) by AFP, because the plasma levels of E2 in these animals affect levels of gonadotropins [9].
• Cellular analysis by in situ hybridization and immunoperoxidase of alpha-fetoprotein and albumin gene expression in rat liver during the perinatal period [30].
• To analyze at the cellular level the decrease in alpha-fetoprotein (AFP) gene expression during the early postnatal growth, we searched for AFP gene transcripts by in situ hybridization using a specific cDNA probe, and for the corresponding protein by immunocytochemistry, on rat liver sections at various times of the perinatal period [30].
• The number of AFP genes obtained in similar titration experiments was approximately 2--3 [31].

References