Modifications in alpha 2u globulin gene structure, transcription, and mRNA translation in hepatomas.

Nakhasi, Hira L.; Lynch, Kevin R.; Dolan, Kevin P.; Unterman, Ronald D.; Antakly, Tony; Feigelson, Philip

doi:10.1016/s0021-9258(19)81018-9

Cited by 23 publications

(2 citation statements)

References 25 publications

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“…Tumor cells often exhibit alterations in the nature of the proteins they synthesize; hepatoma cells, for instance, differ from normal hepatocytes by the loss of certain liver enzymes or by aberrant expression offetal functions or both (1,17,24,30,37). On the other hand, modifications (increase or decrease) in the general level of DNA methylation (19,27) or in the methylation of specific genes (9,25,26,40,42) of tumor cells have been reported. Changes in DNA methylation have been proposed to play an important role in the abnormally regulated expression of tumor cell genes (8,14).…”

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confidence: 99%

“…Rat hepatoma cells show a general decrease in total 5methylcytosine content (19), and in the case ofa-2u globulin, demethylation of the structural gene accompanies the cessation of protein synthesis (25). In contrast, hypermethylation of other rat hepatoma genes (liver-specific proteins or rRNA genes) has been associated with their lack of expression (26,31,40,42).…”

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confidence: 99%

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Spontaneous and 5-Azacytidine-Induced Reexpression of Ornithine Carbamoyl Transferase in Hepatoma Cells

Delers

Szpirer

et al. 1984

Molecular and Cellular Biology

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confidence: 99%

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confidence: 99%

Spontaneous and 5-Azacytidine-Induced Reexpression of Ornithine Carbamoyl Transferase in Hepatoma Cells

Delers

Szpirer

et al. 1984

Molecular and Cellular Biology

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Cellular dynamics of the hormonal and developmental induction of hepatic alpha 2u globulin as demonstrated by immunocytochemistry and specific mRNA monitoring

et al. 1982

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This immunoperoxidase study identifies the hepatocytes that synthesize alpha 2u globulin during male ontogeny and other endocrine states wherein its synthesis is modulated. To correlate biochemical parameters with the immunocytochemistry, alpha 2u globulin mRNA (alpha 2u mRNA) sequences were evaluated by Northern blot hybridization and Rot analysis to a cloned alpha 2u globulin cDNA probe and the functional level of this mRNA measured by cellfree translation. Alpha 2u globulin and its mRNA were detectable in the liver only after male rats reached puberty. During its developmental and hormonal induction, marked heterogeneity was observed; centrolobular hepatocytes showed the strongest staining, whereas periportal hepatocytes were devoid of, or weakly stained for, this protein. This difference between centrolobular and periportal hepatocytes was enhanced during development. Mature male rats exhibited the strongest staining reaction and the highest levels of hepatic alpha 2u globulin mRNA. Almost all hepatocytes in the adult male were stained; however, centrolobular ones were remarkably more stained than periportal ones. Female rat liver was devoid of this protein and of its mRNA. Following androgen administration to castrated female rats, or hydrocortisone administration to adrenalectomized male rats, the alpha 2u globulin mRNA level as well as the number and intensity of centrolobular alpha-2u-globulin-staining hepatocytes were increased in parallel. Following hypophysectomy, almost no alpha 2u globulin could be localized; likewise its mRNA was undetectable. However, when hypophysectomized adult male rats were treated with growth hormone, testosterone, thyroid hormone, and hydrocortisone, the hepatic immunocytochemical staining as well as the level of alpha 2u globulin mRNA sequences and of functional alpha 2u globulin mRNA, and the in vivo biosynthetic rate of alpha 2u globulin, became comparable to that of intact mature male rats. These studies indicate functional heterogeneity among hepatocytes which seems to be determined by their anatomical location within the hepatic lobule. Furthermore, hormonal and developmental induction of alpha 2u globulin involves both an increase in the number of hepatocytes committed to its synthesis and an increase in the rate of its synthesis in already committed cells. These events are accompanied by a concurrent increase in the hepatic alpha 2u globulin mRNA level.Alpha 2u globulin is a protein of unknown function which is synthesized in the livers of male rats after puberty (Roy and Neuhaus, 1966). It is secreted into the serum and is excreted in the urine. The synthesis of this propressed upon administration of estrogen to males (Roy and Neuhaus, 1966;Feigelson and Kurtz, 1978). In addition to androgen, glucotein is undetectable in female rat liver; its synthesis can be induced by administration of androgens to castrated female rats and re-

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Differentially expressed transcripts in neoplastic hepatic nodules and neonatal rat liver studied by cDNA microarray analysis

Tellgren

Wood

Flores‐Morales

et al. 2003

Intl Journal of Cancer

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The molecular mechanisms underlying hepatocarcinogenesis remain unclear. Wistar rats treated with 2-AAF develop hepatocarcinoma in histologically well-characterised stages. In our study, cDNA microarrays were used to measure the expression of 3,000 genes during the progression of liver carcinogenesis in persistent neoplastic nodules. Because tumours frequently revert into a more poorly differentiated phenotype, we also studied the expression of the same set of transcripts in neonatal rat liver. Approximately 2,000 transcripts gave a detectable signal in experiments comparing gene expression in nodules and control tissue. Approximately 8% of these were identified as differentially expressed in liver nodules. The differentially expressed genes fell into several categories with putative or demonstrated roles in signal transduction, metabolism, detoxification, cell-structure and transport. Many of the differentially expressed genes in nodules were not previously known to be regulated during liver carcinogenesis. A universal transcript profile for gene expression in hepatic liver nodules and neonatal liver has been created.

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Modifications in alpha 2u globulin gene structure, transcription, and mRNA translation in hepatomas.

Cited by 23 publications

References 25 publications

Spontaneous and 5-Azacytidine-Induced Reexpression of Ornithine Carbamoyl Transferase in Hepatoma Cells

Spontaneous and 5-Azacytidine-Induced Reexpression of Ornithine Carbamoyl Transferase in Hepatoma Cells

Cellular dynamics of the hormonal and developmental induction of hepatic alpha 2u globulin as demonstrated by immunocytochemistry and specific mRNA monitoring

Differentially expressed transcripts in neoplastic hepatic nodules and neonatal rat liver studied by cDNA microarray analysis

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