The roles of the simian virus 40 tumor antigens in transformation of chinese hamster lung cells

Martin, Robert G.; Setlow, Valerie Petit; Edwards, Carol A.; Vembu, Devi

doi:10.1016/0092-8674(79)90271-x

Cited by 162 publications

(121 citation statements)

References 20 publications

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“…Cysteine-rich repeated segments are also found in the small t antigens of the polyomaviruses including SV40, polyoma, and BK. A number of studies have indicated a role for SV40 small t antigen in transformation and anchorage-independent growth (31,32).…”

Section: Discussionmentioning

confidence: 99%

Bovine papillomavirus contains multiple transforming genes.

Yi¹,

Okayama²,

Howley³

1985

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

232

202

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Bovine papillomavirus type 1 (BPV-1) and its cloned full-length DNA can transform rodent cells in vitro, and the viral DNA persists as an extrachromosomal multicopy plasmid in these transformed cells. Previous studies have identified at least five discrete viral RNAs that are expressed in BPV-1 transformed cells and have shown that these transcripts share a 3' coterminus. To further define the structure of these RNAs and to characterize the functions of individual viral transcripts, we constructed a cDNA library with mRNA from BPV-1-transformed mouse C127 cells using an Okayama and Berg plasmid. From a library of 105 independent clones, 200 BPV-1 specific clones were isolated and characterized. Sequence analysis has revealed differential splicing patterns for the mRNA species in BPV-1 transformed cells. In conjunction with the open reading frames (ORFs) deduced from the BPV-1 DNA sequence, it is possible to predict the structure of the potential encoded proteins. The vector used to generate these cDNA clones contains mammalian cell transcriptional regulatory elements, facilitating their functional characterization. We have identified two distinct classes of cDNA clones that can each independently transform mouse C127 cells. One class of cDNA clones contains the-E2 ORF intact and the second contains the E6 ORF intact. These two putative viral functions appear to act synergistically in transforming mouse C127 cells in vitro.fied several regions of BPV-1 genome that influence the expression of the viral transforming functions (9-12). Deletion mutants affecting the E2 ORF are significantly impaired in their ability to transform mouse C127 cells, suggesting that the putative E2 protein is an important transforming protein (9). The expression of E2 alone, however, is not sufficient for the fully transformed phenotype. Deletion mutagenesis studies map an additional function that is critical for the fully transformed phenotype to the region between the Hpa I site (base 1) and the Sma I site (base 945) (9). These previous studies did not distinguish whether these two distinct regions of the viral genome encode separate proteins or whether they contain exons that are spliced together at the level of mRNA to generate a single transforming protein.To further define the structure of the mRNAs in transformed cells and to characterize the functions encoded by individual viral transcripts, we constructed a cDNA library using mRNA from BPV-1-transformed mouse cells. The vector used for cDNA cloning contains the simian virus 40 (SV40) early promoter, the SV40 late region introns, and the SV40 late region polyadenylylation site, allowing expression of cDNA clones in mouse cells for functional analysis (17). In this study, expression vectors that carried individual cDNA inserts were tested for their ability to transform mouse C127 cells.

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Section: Discussionmentioning

confidence: 99%

Bovine papillomavirus contains multiple transforming genes.

Yi¹,

Okayama²,

Howley³

1985

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

232

202

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“…Small tag cooperates with large Tag in transformation by reducing serum dependence of transformed cells (Bouck et al, 1978;Sleigh et al, 1978;Martin et al, 1979;Frisque et al, 1980). Indeed, a low efficiency of stable transformation and a reduced incidence of tumors with a longer latency period was observed with BKV-IR (Pagnani et al, 1986), a BKV strain bearing a deletion of 253 bp which removes sequences coding for the carboxyl-terminus of small tag (Caputo et al, 1983).…”

Section: Role Of Bkv Tumor Antigens In Transformation and Oncogenicitymentioning

confidence: 99%

Oncogenic transformation by BK virus and association with human tumors

et al. 2003

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BK virus (BKV), a human polyomavirus closely related to JC virus and Simian Virus 40, is ubiquitous in human populations worldwide. After primary infection, BKV establishes a lifelong latent infection in many organs. BKV transforms rodent cells to the neoplastic phenotype and is highly oncogenic in rodents. This review considers the oncogenic potential of BKV in humans and its possible involvement in human tumors. BKV sequences and T antigen (Tag) are detected in several types of human neoplasms, although the viral load is generally low, with less than one copy of the viral genome per cell. The possible causative role of BKV in human oncogenesis rests on the ability of BKV Tag to inactivate the functions of tumor suppressor proteins p53 and pRB family as well as on its ability to induce chromosomal aberrations in human cells. A 'hit and run' mechanism and secretion of paracrine growth factors by BKV Tag-positive cells, recruiting into proliferation neighboring and distant cells, are discussed as possible BKV pathogenic elements in human oncogenesis.

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“…6C) 70). Subsequently, use of conditional or deletion mutants and cloned DNA fragments demonstrated that both of the T antigens encoded by the early region were necessary and sufficient for transformation (10,29,70 (22,39,60,65,70 45,53,59,70). This difference between the type A and N transformants may be attributable to a partial stabilization of the newly synthesized large T antigen in the A-type transformants at the nonpermissive temperature (22).…”

mentioning

confidence: 99%

Recombinant retroviruses encoding simian virus 40 large T antigen and polyomavirus large and middle T antigens.

Jat¹,

Cepko²,

Mulligan³

et al. 1986

Mol. Cell. Biol.

169

112

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We used a murine retrovirus shuttle vector system to construct recombinants capable of constitutively expressing the simian virus 40 (SV40) large T antigen and the polyomavirus large and middle T antigens as well as resistance to G418. Subsequently, these recombinants were used to generate cell lines that produced defective helper-free retroviruses carrying each of the viral oncogenes. These recombinant retroviruses were used to analyze the role of the viral genes in transformation of rat Flll cells. Expression of the polyomavirus middle T antigen alone resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were unaltered by the criteria of morphology, anchorageindependent growth, and tumorigenicity. More surprisingly, SV40 large T-expressing cell lines were not tumorigenic despite the fact that they contained elevated levels of cellular p53 and had a high plating efficiency in soft agar. These results suggest that the SV40 large T antigen is not an acute transforming gene like the polyomavirus middle T antigen but is similar to the establishment genes such as myc and adenovirus EIa.The DNA tumor viruses polyomavirus (Py) and simian virus 40 (SV40) are both capable of transforming both primary and established cell lines in vitro (for a review see reference 70). Extensive work has shown that genes encoded by the early regions of these viruses are both necessary and sufficient for transformation (1,10,12,14,15,18,29,38,43,49,67; for a review see reference 70). Analysis of the respective roles of these genes has been complicated because the early regions are multiply spliced to specify more than one protein: Py encodes three antigens, the large T (100 kilodaltons [kDa]), the middle T (56 kDa), and the small T (22 kDa) (20,21,24,25,58); SV40 encodes two antigens, the large T (95 kDa) and the small T (20 kDa) (48,51,69). In addition, transformation assays with DNA tumor viruses have generally involved infection or transfection of a cell population and selection of a small fraction of cells with a particular phenotype. For example, this selection could be based on either focus formation, anchorage-independent growth, or growth in low serum, and thus, this type of assay does not necessarily reveal the average phenotype resulting from interaction of the oncogene with the cell. Moreover, the process by which the viral DNA segment integrates into cellular chromosomes can give rise to multiple copies and rearrangements. The resulting variation in levels of viral mRNA and gene expression can significantly affect the range of phenotypes of the transformants. Previous studies of the variation in phenotype observed after transformation by SV40 detected clonal cell lines that ranged over completely, partially, or minimally transformed (50, 56).We therefore undertook a systematic analysis of the role of the various genes encoded by the early regions of these viruses by isolating cell lines which constitutively express these proteins without prior selection ...

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The roles of the simian virus 40 tumor antigens in transformation of chinese hamster lung cells

Cited by 162 publications

References 20 publications

Bovine papillomavirus contains multiple transforming genes.

Bovine papillomavirus contains multiple transforming genes.

Oncogenic transformation by BK virus and association with human tumors

Recombinant retroviruses encoding simian virus 40 large T antigen and polyomavirus large and middle T antigens.

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