Anomaly of Aldolase in Primary Liver Cancer

Schapira, F; Dreyfus, Jean‐Claude; Schapira, G

doi:10.1038/200995a0

Cited by 117 publications

(31 citation statements)

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“…During the development of the malignant state, the neoplastic cell becomes increasingly refractory to both the internal and external stimulae which integrate its normal counterparts into functional tissues and organ systems. This lack of integration is associated with alterations in the expression of a host of gene products, including, for example, the ectopic biosynthesis of hormones (Rees, 1975; Imura, 1980), various nuclear modifications (Rovera, 1975;Sarma et al, 1975), changes in enzyme and isozyme patterns (Weinhouse, 1970, Weinhouse et al, 1972Ibsen, 1977;Ghosh et al, 1978;Foti et al, 1977;Greengard & Herzfeld, 1977;Shapira et al, 1963), appearance of foetal antigens (Gold, 1971) and cell surface modifications (Robin & Nicholson, 1975;Mora, 1974). It is thus clear that a powerful interference with the normal machinery of gene expression accompanies the transformed state.…”

mentioning

confidence: 99%

5-Methylcytosine depletion during tumour development: An extension of the miscoding concept

Nyce¹,

Weinhouse²,

Magee³

1983

Br J Cancer

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Perhaps the most ubiquitous aspect of tumours and the neoplastic cells of which they are composed is their loss of the ability to control cellular functions in a normal way. During the development of the malignant state, the neoplastic cell becomes increasingly refractory to both the internal and external stimulae which integrate its normal counterparts into functional tissues and organ systems. This lack of integration is associated with alterations in the expression of a host of gene products, including, for example, the ectopic biosynthesis of hormones (

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mentioning

confidence: 99%

5-Methylcytosine depletion during tumour development: An extension of the miscoding concept

Nyce¹,

Weinhouse²,

Magee³

1983

Br J Cancer

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“…The The study of the expression of aldolase B is of particular interest. Regulation of the aldolase genes is altered in hepatoma cells (13,14). In transformed liver cells production of the adult isozyme, B, is shut off and the embryonic form, aldolase A, is produced again.…”

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Complete amino acid sequence for human aldolase B derived from cDNA and genomic clones.

Rottmann¹,

Tolan²,

Penhoet³

1984

Proc. Natl. Acad. Sci. U.S.A.

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Several aldolase B clones from a human liver cDNA library have been identified by using a rabbit aldolase A cDNA as a hybridization probe. The most complete of these, pHL413, is 1389 base pairs long and covers -80% of the length of the mRNA, including 90% of the translated region. The cDNA, pHL413, was used to identify a genomic clone, XHG313, which encoded the remaining amino acids of human aldolase B. We demonstrate that the amino acid and nucleotide sequences of aldolase are strongly conserved even between different isozymes. Furthermore, in the 3'-untranslated regions of the mRNAs for the B isozyme of human and rat there is an extensive stretch of homology. Aldolase B lacks a cysteine at positions 72 and 338 and lacks a histidine at position 361. These residues, which are present in rabbit aldolase A, have previously been proposed to take part in catalysis. Our findings suggest that this may not be the case.Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a glycolytic enzyme that catalyzes the reversible conversion of fructose 1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The enzyme consists of a tetramer of identical 40,000-dalton subunits. In vertebrates, three isozyme forms exist. These can be distinguished by their electrophoretic and catalytic properties (1). The amino acid sequence of the region around the active site lysine has been determined for aldolases from several sources (2-8). The similarities among these sequences suggest that the amino acid sequence of aldolase is greatly conserved throughout vertebrate evolution. The differences show that they are indeed distinct proteins, the products of a family of related genes. The study of the genes for this enzyme is of interest because the expression of isozyme forms is regulated during development and because they represent a poorly characterized class of genes, the so-called "housekeeping genes," which are expressed in all cells.Mammalian tissues express the aldolase isozymes in a well-characterized pattern (9). The The study of the expression of aldolase B is of particular interest. Regulation of the aldolase genes is altered in hepatoma cells (13,14). In transformed liver cells production of the adult isozyme, B, is shut off and the embryonic form, aldolase A, is produced again. Furthermore, in humans deficiencies of aldolase B result in a genetic disorder, hereditary fructose intolerance (15, 16). Determination of the nature of the defect(s) that cause hereditary fructose intolerance at the genetic level and investigation of the regulation of the gene during development and oncogenesis require nucleic acid probes specific for aldolase B.This paper describes the isolation and characterization of several cDNA clones for human aldolase B. From the nucleotide sequence of the cDNAs and a genomic clone, we deduce the entire amino acid sequence for this previously uncharacterized protein. This information allows us to confirm the existence of a high degree of homology between the aldolase isozymes throughou...

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“…Carcinogenesis is associated with very early histological and biochemical alterations : necrosis of hepatocytes with appearance of new cellular populations and, simultaneously, resurgence of foetal proteins and a decrease in the expression of adult specific markers as shown first by Schapira et al for aldolase [2] and then later extended to other enzymes and proteins [3 -171. Aldolase B [7, 81 and L-type pyruvate kinase [9, I51 are characteristic of normal adult liver and are decreased in hepatoma cells, while the foetal-type isozymes, aldolases A and C, and M2-type pyruvate kinase increase [7,8,[10][11][12] 151. a-Foetoprotein, a foetal equivalent of serum albumin, is also re-expressed during hepatocarcinogenesis [ 5 , 6, 13, 141.…”

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Modifications of the expression of liver‐specific and non‐specific messenger RNAs during azo‐dye hepatocarcinogenesis

Lamas

Schweighoffer

van

et al. 1985

European Journal of Biochemistry

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The expression of specific and non-specific rat liver messenger RNAs has been studied during 3'-methyl-4-(dimethy1amino)azobenzene (3'-MeDAB) carcinogenesis, using cDNA probes complementary to inRNAs encoding aldolase A and B, L-type pyruvate kinase, albumin, a-foetoprotein, transferrin and an unidentified 2.7 x 103-base mRNA. mRNAs specific for undifferentiated cells, such as those encoding aldolase A and the unidentified 2.7 x 103-base species were re-expressed very early, being easily detectable at the 1st week of 3'-MeDAB treatment. They reached a maximum of expression at the 4th week. Simultaneously the levels of aldolase B and L-type pyruvate kinase mRNAs dramatically decreased as compared to controls, but remained responsive to induction by a high-carbohydrate diet.Albumin and transferrin mRNA levels were only slightly modified in the course of the carcinogenic diet. At the terminal stage of hepatocarcinogenesis, i. e. in malignant hepatoma cells, expression and inducibility of aldolase B and L-type pyruvate kinase mRNAs were similar to those in normal adult rats while mRNAs specific for undifferentiated or foetal stages were also synthesized.The very early changes in gene expression for aldolases A and B, L-type pyruvate kinase and the 2.7 x lo3-base mRNA species could indicate that carcinogenic diet modifies gene control mechanisms long before inducing hepatoma.I t is well established that rats fed a 3'-methyl-4-(dimethy1amino)azobenzene (3'-MeDAB)-containing diet for twenty weeks develop a well-differentiated (slow-growing) hepatoma [I]. Carcinogenesis is associated with very early histological and biochemical alterations : necrosis of hepatocytes with appearance of new cellular populations and, simultaneously, resurgence of foetal proteins and a decrease in the expression of adult specific markers as shown first by Schapira et al. for aldolase [2] and then later extended to other enzymes and proteins [3 -171. Aldolase B [7, 81 and L-type pyruvate kinase [9, I51 are characteristic of normal adult liver and are decreased in hepatoma cells, while the foetal-type isozymes, aldolases A and C, and M2-type pyruvate kinase increase [7,8,[10][11][12] 151. a-Foetoprotein, a foetal equivalent of serum albumin, is also re-expressed during hepatocarcinogenesis [ 5 , 6, 13, 141.The expression of the albumin and a-foetoprotein genes during liver development, regeneration and carcinogenesis has been widely investigated. a-Foetoprotein gene expression switches off at birth and conversely albumin gene expression switches on; phenotypic expression of a-foetoprotein is resumed in the adult rat during regeneration, exposure to chemical hepatocarcinogenes and in hepatoma [I 8 -241.During 3'-MeDAB hepatocarcinogenesis there is re-expression of a-foetoprotein but albumin mRNA is unchanged [24] decreased while aldolase A mRNA increased in carcinogentreated liver [25].However, the mechanisms involved in regulation of isozynie expression are not yet as clearly understood as are those leading to the resurgence of a-foetoprotein....

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Anomaly of Aldolase in Primary Liver Cancer

Cited by 117 publications

References 8 publications

5-Methylcytosine depletion during tumour development: An extension of the miscoding concept

5-Methylcytosine depletion during tumour development: An extension of the miscoding concept

Complete amino acid sequence for human aldolase B derived from cDNA and genomic clones.

Modifications of the expression of liver‐specific and non‐specific messenger RNAs during azo‐dye hepatocarcinogenesis

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