A new avian erythroblastosis virus, AEV-H, carries erbB gene responsible for the induction of both erythroblastosis and sarcomas

Yamamoto, Tadashi; Hihara, Hiroshi; Nishida, Tsutomu; Kawai, Sadaaki; Toyoshima, Kumao

doi:10.1016/0092-8674(83)90153-8

Cited by 130 publications

(65 citation statements)

References 34 publications

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“…For a discussion on the respective merits of the dierent types of progenitors, see Schroeder et al, 1992. Most of the studies were performed using bone marrow cells from 19 days old SPAFAS embryos that were infected as previously described (Gandrillon et al, 1989) with AEV-H (Avian Erythroblastosis Virus-H), a retrovirus carrying the verbB oncogene as the sole oncogene. This virus induces a strong hyper-proliferation of progenitor cells that retain their ability to dierentiate (Yamamoto et al, 1983). Those cells will be referred to as`AEV-H progenitor cells'.…”

Section: Cellsmentioning

confidence: 99%

Role of the different RAR isoforms in controlling the erythrocytic differentiation sequence. Interference with the v-erbA and p135gag-myb-ets nuclear oncogenes

Gandrillon

Samarut

1998

Oncogene

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Little is known as to how the nuclear oncogenes v-erbA and p135gag-myb-ets do transform cells. The elucidation of their molecular mechanisms of action requires the identi®cation of relevant target genes. We analysed the possibility for the RARb gene to represent such a target gene. We ®rst show that the RARb gene induction is a speci®c and direct process, requiring the continous presence of retinoids and under the control of the RARa isoform exclusively. We then show that the expression of either the v-erbA or the p135 gag-myb-ets oncogene is not sucient to block the RARb gene induction. We con®rmed the loss of RARb gene response in certain cell lines but we discarded the possibility that this loss might represent a necessary step for cell lines immortalization. We further show that the RARa isoform activation is necessary and sucient to induce the growth inhibition and the dierentiation stimulation characteristic for the commitment-inducing ability of retinoids in chicken erythrocytic progenitor cells. We therefore propose a model showing that RARa but not RARb is the key mediator for commitment to dierentiation and that it should control two dierent set of genes whose expression is dierentially aected by the verbA and the p135 gag-myb-ets oncogenes.

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Section: Cellsmentioning

confidence: 99%

Role of the different RAR isoforms in controlling the erythrocytic differentiation sequence. Interference with the v-erbA and p135gag-myb-ets nuclear oncogenes

Gandrillon

Samarut

1998

Oncogene

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“…It is not clear which of these mutations is responsible for the sarcomagenic activities of these v-erbB gene products (4,12,15).…”

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confidence: 99%

“…When placed in a retroviral vector or carried by naturally occurring transducing viruses, the IA c-erbB gene induces only erythroleukemia (7)(8)(9)(10). On the other hand, a number of v-erbB genes isolated from acute leukemia viruses have the ability to generate leukemias, sarcomas, and hemangiomas (2,(11)(12)(13)(14). A comparison of the coding sequences of these v-erbB genes [found in the R (ES-4) and H strains ofavian erythroblastosis (AEV)]…”

mentioning

confidence: 99%

Disease tropism of c-erbB: effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation.

Pelley

Maihle

Boerkoel

et al. 1989

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

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Avian leukosis virus induces erythroleukemia in chickens by proviral insertional mutation of the protooncogene c-erbB. The product of the insertionally activated c-erbB locus lacks the extracellular ligand-binding domain and is strictly leukemogenic. It has previously been demonstrated that the disease spectrum associated with aberrant c-erbB expression can be expanded by structural perturbation of the cytoplasmic domain of this protein. In this report, we use mutagenesis and retroviral vectors to identify specific mutations in the carboxyl-terminal domain of the insertionally activated c-erbB product that are sufficient to activate the sarcomagenic potential of this protein. Interestingly, a point mutation in the kinase domain appears to be sufficient for sarcomagenic activation. However, removal of the terminal tyrosine residue of the c-erbB product, implicated in modulating kinase activity, does not lead to a fully transforming phenotype. These studies suggest that there are multiple ways to activate the fibroblast-transforming potential of the insertionally activated c-erbB product. The conformation of this protein may play a more significant role in oncogenic activation than the phosphorylation status of the putative carboxylterminal autophosphorylation site.Avian leukosis virus can induce erythroleukemia by proviral insertional mutagenesis of the protooncogene c-erbB (1,2). The avian c-erbB gene encodes a growth factor receptor that is structurally homologous to the human epidermal growth factor (EGF) receptor (3-5). Proviral integration results in separation of the ligand-binding domain of this receptor from its transmembrane and cytoplasmic domains (6). Transcripts expressed from the proviral insertionally activated c-erbB locus (IA c-erbB) code for an amino-terminal-truncated cerbB gene product that has been postulated to have constitutive tyrosine kinase activity.One fascinating feature ofthe IA c-erbB product is its strict tissue specificity of transformation. When placed in a retroviral vector or carried by naturally occurring transducing viruses, the IA c-erbB gene induces only erythroleukemia (7-10). On the other hand, a number of v-erbB genes isolated from acute leukemia viruses have the ability to generate leukemias, sarcomas, and hemangiomas (2,(11)(12)(13)(14). A comparison of the coding sequences of these v-erbB genes [found in the R (ES-4) and H strains ofavian erythroblastosis (AEV)]with the IA c-erbB coding sequence reveals that the former contain multiple point mutations as well as truncations in their carboxyl-terminal sequences. It is not clear which of these mutations is responsible for the sarcomagenic activities of these v-erbB gene products (4, 12, 15).The carboxyl-terminal domain (arbitrarily defined as the region 3' of the tyrosine kinase domain) of the human EGF receptor contains three tyrosine residues identified as sites of autophosphorylation: the tyrosine residue most proximal to the carboxyl terminus, Tyr-1173, is the major autophosphorylation site (16). Evidence that...

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“…In the case of AEV, analyses of deletion mutants (8,9) and the isolation of an AEV variant, termed AEV-H, that lacks the Agag-erbA gene (27) (7). Since both viruses have similar oncogenic spectra yet each has a specific second gene with potential transforming function, it follows that 8gag-myc is essential for common oncogenic properties (7).…”

mentioning

confidence: 99%

Mutagenesis of avian carcinoma virus MH2: only one of two potential transforming genes (delta gag-myc) transforms fibroblasts.

Zhou¹,

Kan

Papas

et al. 1985

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

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Most directly oncogenic retroviruses contain single, autonomous transforming (onc) genes (1). However, three oncogenic retroviruses contain two genes with oncogenic potential, namely the avian carcinoma viruses MH2 (2-5) and OK10 (6, 7) and avian erythroblastosis virus (AEV) (8, 9). The 5.5-kilobase (kb) RNA genome of MH2 (10) has the genetic structure Agag-mht-myc (2-5). One of the two genes with potential transforming function encoded by MH2 is a 3-kb Agag-mht gene, defined by a p100 protein product (11). A close structural relative of this gene (5, 12) is the only transforming gene of murine sarcoma virus MSV 3611 (13).The other MH2 gene is a myc-related gene, termed 8gag-myc, which is discontiguous. This gene includes a gag-derived 5' exon of only six gag codons (therefore 8gag) and a 3' 1.6-kb myc exon that is colinear with the two 3'-terminal exons of chicken proto-myc (5, 14). This gene is expressed via a subgenomic 2.6-kb mRNA as a 57,000-dalton (p57) protein product (15-18). The 7.5-kb RNA genome of OK10 virus (19) contains two overlapping myc-related genes (7); a contiguous gag-Apol-myc gene, which encodes a p200 protein; and a discontiguous 8gag-myc gene, which as in MH2 is also expressed as a subgenomic 3.5-kb mRNA encoding a p57protein (6,17,18 Here we analyze MH2 to determine whether it could serve as a model for multigene carcinogenesis. Several lines of evidence indicate that the 8gag-myc gene of MH2 is necessary for oncogenicity and that it transforms fibroblasts without Agag-mht as helper gene. (1) The 8gag-myc gene of MH2 is shared by MH2 and OK10 (7). Since both viruses have similar oncogenic spectra yet each has a specific second gene with potential transforming function, it follows that 8gag-myc is essential for common oncogenic properties (7).(ii) A study that has isolated MH2-transformed fibroblasts that express high levels of the 8gag-myc product p57 but no detectable Agag-mht product pl00 has concluded that p57 is sufficient for transforming function (15 6389The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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A new avian erythroblastosis virus, AEV-H, carries erbB gene responsible for the induction of both erythroblastosis and sarcomas

Cited by 130 publications

References 34 publications

Role of the different RAR isoforms in controlling the erythrocytic differentiation sequence. Interference with the v-erbA and p135gag-myb-ets nuclear oncogenes

Role of the different RAR isoforms in controlling the erythrocytic differentiation sequence. Interference with the v-erbA and p135gag-myb-ets nuclear oncogenes

Disease tropism of c-erbB: effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation.

Mutagenesis of avian carcinoma virus MH2: only one of two potential transforming genes (delta gag-myc) transforms fibroblasts.

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