Abelson murine leukemia virus-infected cell lines defective in transformation

Sacks, Thomas L.; Hershey, Elizabeth J.; Stephenson, John

doi:10.1016/0042-6822(79)90335-0

Cited by 25 publications

(18 citation statements)

References 11 publications

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“…Those in the first class are induced by inactivation of the oncogenes. Those in the second class are induced by inactivation of cellular target genes (13,20,25,32,37) or cooperating genes (14) required for transformation by a given oncogene. The third class of revertants results from activation of dominant transformation suppressor genes (18).…”

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confidence: 99%

Resistance to oncogenic transformation in revertant R1 of human ras-transformed NIH 3T3 cells.

et al. 1989

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A flat revertant, Rl, was isolated from humgn activated c-Ha-ras-1 (hu-ac-Ha-ras) gene-transformed NIH 3T3 cells (EJ-NIH 3T3) treated with mutagens. Rl contained unchanged transfected hu-ac-Ha-ras DNA and expressed high levels of hu-ac-Ha-ras-specific mRNA and p21 protein. Transfection experiments revealed that NIH 3T3 cells could be transformed by DNA from Rl cells but Rl cells could not be retransformed by Kirsten sarcoma virus, DNA from EJ-NIH 3T3 cells, hu-ac-Ha-ras, v-src, v-mos, simian virus 40 large T antigen, or polyomavirus middle T antigen. Somatic cell hybridization studies showed that RI was not retransformed by fusion with NIH 3T3 cells and suppressed anchorage independence of EJ-NIH 3T3 and hu-ac-Ha-ras gene-transformed rat W31 cells in soft agar. These results suggest that the reversion and resistance to several oncogenes in Rl is due not to cellular defects in the production of the transformed phenotype but rather to enhancement of cellular mechanisms that suppress oncogenic transformation.It has been found that 10 to 20% of human tumors have a mutation in one of the three ras oncogenes (Ha-ras, Ki-ras and N-ras) leading to the production of p21 ras oncoproteins, which are thought to play an important role in the transformed phenotype (1). The ras proteins bind GTP and GDP and have intrinsic GTPase activity. They may control cell proliferation by regulating a signal transduction pathway as do the regulatory G proteins (1). However, the biochemical mode of action and the biological target molecules of the ras proteins are unknown. Recently, the activating mutations of the ras genes have been detected not only in malignant tumors such as colorectal tumors but also in benign tumors such as colon adenomas (3, 9). The former showed somatic loss of chromosome sequences, but the latter did not (8). Such chromosomal changes as monosomy or trisomy were also described in hamster cells transfected with v-Ha-ras or human activated c-Ha-ras-1 (hu-ac-Ha-ras) genes (23,31). All of these findings suggest that ras activation is not sufficient and that alteration of cellular transformation suppressor genes is necessary for malignant transformation of cells. However, little is known about the suppressor genes or their products. Isolation of mutant cells that contain alterations in one or more of the suppressor genes involved in transformation by oncogenes could be one approach to this problem.The EJ-NIH 3T3 cell line, which is an NIH 3T3 cell line carrying the transfected hu-ac-Ha-ras sequence of EJ human bladder carcinoma cells, kindly provided by T. Y. Shih (National Cancer Institute, Frederick, Md.; 34) showed the typical morphology of transformed cells. EJ-NIH 3T3 cells (106) were treated with ethyl methanesulfonate (200 ,ug/ml for 24 h) and 8-azaguanine (5 ,ug/ml). Two mutant clones, Rl and R2, were selected from the population. They showed a flat, typical spindle shape and an ordered growth pattern of fibroblast or endothelial cells. They had lost the ability to pile up at random and became contact inhibited ...

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confidence: 99%

Resistance to oncogenic transformation in revertant R1 of human ras-transformed NIH 3T3 cells.

et al. 1989

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“…Analysis of cells nonproductively transformed by FeSV (47), AbMuLV (44), or AK-T8 (45) revealed the presence of 2S,OOO-molecular-weight polyproteins containing pIS and pl2 antigenic reactivity as well as variable levels of jNCI, VOL. 63. NO.…”

Section: High-molecular-weight Polyproteins En-coded By Replication-dmentioning

confidence: 99%

“…One line of evidence favoring this possibility is based on genetic studies in which a number of morphologic revertants of mink cells transformed by Ab-MuLV (63) or FeSV (Blennerhassett GT, Stephenson JR: Unpublished data) have been generated. Such mutants have been shown to be defective in cellular genes influencing expression of transformation rather than in the recombinant viral genomes (63). As summarized in table 3, loss of morphologic transformation in such mutant clones is associated with loss of polyprotein expression, thus favoring the possibility that polyprotein expression is a requirement for expression of transformation.…”

Section: 'Mgppp-{)lalbl(c)~1vv3'mentioning

confidence: 99%

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Type C Retroviruses as Vectors for Cloning Cellular Genes With Probable Transforming Function<xref ref-type="fn" rid="FN4">4</xref>

1979

JNCI: Journal of the National Cancer Institute

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“…In the case of A-MuLV (and other defective transforming retroviruses) there are no linked functional replication genes that can be used in the section of td mutants. As an alternative one can search for cells that express A-MuLV antigens but are not transformed (21). By such screening procedures, we have isolated a spontaneous td mutant of A-MuLV.…”

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confidence: 99%

A transformation-defective mutant of Abelson murine leukemia virus lacks protein kinase activity.

Witte¹,

Goff²,

Rosenberg³

et al. 1980

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

108

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A transformation-defective mutant of Abelson murine leukemia virus (A-MuLV), called A-MuLV-P92td, has been isolated. The mutant encodes a serologically identifiable A-MuLV protein of molecular weight 92,000 (P92) but it lacks the ability to transform either fibroblasts or bone marrow lymphoid cells. In contrast to the protein made by transforming strains of A-MuLV, the protein made by A-MuLV-P92td does not becme phosphorylated during in vitro incubation with [gamma-32P]ATP. If the protein is mixed with proteins from cells transformed by a functional A-MuLV strain, phosphorylation of P92 occurs, showing that its ability to accept phosphate is not altered by the mutation. These parallel changes provide genetic evidence that the A-MuLV protein is a transforming protein and that its associated protein kinase activity (EC 2.7.1.37) is a crucial part of its transforming ability.

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Abelson murine leukemia virus-infected cell lines defective in transformation

Cited by 25 publications

References 11 publications

Resistance to oncogenic transformation in revertant R1 of human ras-transformed NIH 3T3 cells.

Resistance to oncogenic transformation in revertant R1 of human ras-transformed NIH 3T3 cells.

Type C Retroviruses as Vectors for Cloning Cellular Genes With Probable Transforming Function<xref ref-type="fn" rid="FN4">4</xref>

A transformation-defective mutant of Abelson murine leukemia virus lacks protein kinase activity.

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