Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha-Fetoprotein (AFP) is a well-established cell differentiation and tumor marker. We showed previously that McA-RH 7777 hepatoma cells are heterogeneous in terms of their AFP cellular expression. In the present study, we developed stable and unstable 7777 hepatoma clones in terms of their AFP phenotype: AFP-producing (AFP+) or AFP-nonproducing (AFP-) clones, and investigated in these clones (a) AFP phenotype related to protein and mRNA levels; (b) cellular morphology; and (c) expression of several liver-specific markers. Our results demonstrated that alpha-albumin expression paralleled that of AFP, from the absence of alpha-albumin message in AFP- clones to high expression in AFP+ clones, suggesting that common mechanisms control the expression of both proteins in this hepatoma cell population. In addition, the karyotypes of the McA-RH 7777 hepatoma cell line and its 15 generated clones were analyzed and correlated to their AFP phenotypes. Only the stable AFP+ clones showed homogeneously staining regions on the chromosome carrying the AFP gene. These results strongly suggest that amplification of either structural or regulatory sequences of the AFP gene is involved in maintaining its high expression.
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PMID:Alpha-fetoprotein (AFP) expression in clones of McA-RH 7777 rat hepatoma: correlation with the occurrence of homogeneously staining regions on chromosome 14. 754 18

The alpha1-fetoprotein (AFP) gene is located between the albumin and alpha-albumin genes and is activated by transcription factor FTF (fetoprotein transcription factor), presumed to transduce early developmental signals to the albumin gene cluster. We have identified FTF as an orphan nuclear receptor of the Drosophila FTZ-F1 family. FTF recognizes the DNA sequence 5'-TCAAGGTCA-3', the canonical recognition motif for FTZ-F1 receptors. cDNA sequence homologies indicate that rat FTF is the ortholog of mouse LRH-1 and Xenopus xFF1rA. Rodent FTF is encoded by a single-copy gene, related to the gene encoding steroidogenic factor 1 (SF-1). The 5.2-kb FTF transcript is translated from several in-frame initiator codons into FTF isoforms (54 to 64 kDa) which appear to bind DNA as monomers, with no need for a specific ligand, similar KdS (approximately equal 3 x 10(-10) M), and similar transcriptional effects. FTF activates the AFP promoter without the use of an amino-terminal activation domain; carboxy-terminus-truncated FTF exerts strong dominant negative effects. In the AFP promoter, FTF recruits an accessory trans-activator which imparts glucocorticoid reactivity upon the AFP gene. FTF binding sites are found in the promoters of other liver-expressed genes, some encoding liver transcription factors; FTF, liver alpha1-antitrypsin promoter factor LFB2, and HNF-3beta promoter factor UF2-H3beta are probably the same factor. FTF is also abundantly expressed in the pancreas and may exert differentiation functions in endodermal sublineages, similar to SF-1 in steroidogenic tissues. HepG2 hepatoma cells seem to express a mutated form of FTF.
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PMID:The alpha1-fetoprotein locus is activated by a nuclear receptor of the Drosophila FTZ-F1 family. 866 3

The potential association of alpha-albumin (ALF) with hepatocellular carcinoma (HCC) was investigated. Expression of ALF was significantly reduced in HCC tumor tissue as compared with the paired peritumor tissue from 16 patients and in four HCC cell lines as compared with normal hepatocytes. ALF mRNA was also down-expressed in circulating HCC cells compared to circulating normal hepatocytes. The proliferation of Hep3B cells was inhibited by over-expression of ALF. Taken together, ALF is significantly down-regulated in HCC, and this might facilitate the proliferation of HCC. Thus, detection of ALF mRNA, in addition to that of alpha-fetoprotein (AFP) mRNA, might help to distinguish normal or malignant hepatocytes in peripheral blood.
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PMID:Significant down-regulation of alpha-albumin in human hepatoma and its implication. 1105 53