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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous reports have demonstrated that E7 is the major transforming gene of HPV-16 and that continued expression of the gene is required to maintain the transformed phenotype of primary baby rat kidney cells transformed by HPV-16 E7 and EJ-ras. To investigate the point of action of E7 in the cell cycle we have utilised a system of inducible expression of the E7 gene. The studies reported here show that stimulation of cellular DNA synthesis by E7 is distinct from that observed with calf serum. In combination with cytofluorimetric analyses these results indicate that E7 functions at the transition from G1 to S phase of the cell cycle. This adds further support to the hypothesis of a common pathway of transformation shared by the DNA tumour viruses HPV, SV40 and Adenovirus.
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PMID:HPV-16 E7 functions at the G1 to S phase transition in the cell cycle. 235 20

NM23, a novel gene associated with low tumor metastatic potential, has been investigated in an experimental system in which metastasis is inhibited by the transfection of viral and cellular oncogenes. The experimental system utilizes transfection of the Adenovirus 2 Ela gene to inhibit metastasis: rat embryo fibroblasts (REF) transfected with c-Ha-ras were highly metastatic, while REF cotransfected with ras and Ela were virtually nonmetastatic. NM23 RNA levels were higher in three independently ras + Ela-cotransfected, low metastatic REF lines than in three independently ras-transfected, highly metastatic REF line. Differences in hybridizable NM23 RNA levels between the two groups of transfected cell lines ranged from 2- to 8-fold. In situ hybridization demonstrated that the relatively high NM23 RNA levels in low metastatic ras + Ela-cotransfected REF cells were not due to overexpression of the NM23 gene by a subpopulation of cells. Thus, the metastasis-inhibitory effect of the exogenously added Ela gene has been associated with increased activation of the cellular NM23 gene. This associated is particularly significant in light of the very few changes observed in translatable steady-state RNA levels between ras- and ras + Ela-transfected REF lines. The data identify NM23 as a candidate for a gene that suppresses the malignant state.
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PMID:Altered expression of NM23, a gene associated with low tumor metastatic potential, during adenovirus 2 Ela inhibition of experimental metastasis. 246 Feb 24

Cell fusion experiments have predicted the existence of cancer metastasis suppressor genes. The E1a gene of Adenovirus 2 has been demonstrated to suppress c-Ha-ras induction of experimental metastatic potential in rat embryo fibroblasts. Another approach to the identification of candidate metastasis suppressor genes has utilized differential or subtraction hybridizations to clone genes which are downregulated as cells become highly metastatic. To date, three such genes have been identified: nm23, WDNM1, and fibronectin. With regard to nm23, downregulation of nm23 RNA levels in high metastatic potential cells has been demonstrated in a wide variety of rodent metastasis systems, including K-1735 murine melanoma cell lines, nitrosomethylurea-induced rat mammary tumors, MMTV-induced mouse mammary tumors, and ras +/- E1a transfected rat embryo fibroblasts. Whether the expression of the nm23 gene, and other down-regulated genes in tumor metastasis, correlates with changes in metastatic potential, or actually has suppressive activity, will require transfection experiments.
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PMID:Search for metastasis suppressor genes. 253 85

Viruses are becoming increasingly recognized as a major etiological agent in the development of numerous forms of human cancer. Human papillomaviruses (HPVs) have been associated with a number of neoplastic lesions, most notably cervical cancer which is one of the major forms of cancer world wide. Of the over 50 types of identified HPVs, HPV types 16, 18, 31 and 33 are the types most commonly associated with malignant carcinomas. These viruses contain double stranded DNA which code for about eight gene products, some of which are oncogenic when introduces into cultured rodent or human cells. In particular, both the E6 and E7 gene products have different oncogenic capabilities and these genes are selectively retained within the genome of cervical carcinoma derived cells. The E7 gene product has immortalizing capabilities in primary cells and is able to cooperate with an activated ras oncogene to fully transform primary rodent cells. The E7 gene product from HPV type 16 is also capable of complexing in vitro to the anti-oncogene product, Rb. Similar complexes occur with Adenovirus E1A and SV40 large T proteins which may suggest a shared mechanism of transformation used by HPV type 16, Adenovirus and SV40. Transformation studies using primary human cells and nontumorigenic HeLa/fibroblast hybrid cells have also suggested that chromosome 11 may be important in suppressing the HPV transformed phenotype. The transformed phenotype may therefore also involve an impaired intracellular control of persisting HPV oncogenic sequences. Although there exists no solid evidence that a cytotoxic T-lymphocyte reaction is mounted against HPV transformed cells, there is evidence that both NK cells and activated macrophages can preferentially kill HPV transformed cells in vitro. Future studies are required to identify possible targets present on HPV transformed cells which are absent on normal cells.
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PMID:The cell biology of human papillomavirus transformed cells. 255 72

Cells of the established REF52 line completely resist stable transformation by activated ras oncogenes, apparently because expression of ras p21 above a low threshold level inhibits cell proliferation. Adenovirus E1A and simian virus 40 (SV40) large T antigen enable ras oncogenes to transform REF52 cells and therefore protect REF52 cells from ras-induced growth arrest. The present study investigated the role of c-myc in regulating the responses of REF52 cells to ras oncogenes. We report that transcriptionally activated c-myc oncogenes enabled ras to transform REF52 cells but the efficiency of transformation was 20- to 30-fold lower than with E1A. In contrast, myc and E1A were similarly active as ras collaborators when assayed on primary baby rat kidney (BRK) cells. Relative difficulties transforming REF52 celis by myc and ras did not result from a requirement to express either gene at higher levels in REF52 as compared with BRK transformants. Steady state levels of endogenous c-myc RNA were unaltered in REF52 cells transformed by ras together with c-myc, E1A or SV40 large T antigen. Furthermore, ras-induced growth arrest was not accompanied by a decline in c-myc RNA levels. These results suggest that transcriptional control of c-myc is not affected either by the anti-proliferative effects of ras or by the collaborating activities of E1A and SV40 large T antigen.
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PMID:Role of c-myc in the transformation of REF52 cells by viral and cellular oncogenes. 283 May 82

Adenovirus serotype 5 E1a proteins immortalize primary cells and in cooperation with products of a second oncogene, such as adenovirus serotype 5 E1b or EJ ras, produce full transformation. E1a also activates transcription of specific viral and cellular promoters, represses enhancer-dependent genes, and induces cellular DNA synthesis in quiescent cells. Comparison of different adenovirus serotypes has identified three conserved regions in the E1a protein sequence. We have analyzed E1a mutants with deletions-linker insertions in or preceding the first conserved region, region 1 (amino acids 40 through 77 of adenovirus serotype 5 E1a). E1a mutants which have in-frame deletions-substitutions in region 1 or pre-region 1 sequences were reconstructed into adenovirus to yield a total of 14 mutant viruses. All the mutant viruses showed wild-type growth in HeLa cells, confirming that region 1 is nonessential in these cells. However, we show that region 1 provides two distinct functions in infected primary rodent cells. One function is essential for induction of cell DNA synthesis, and the other is essential for focus formation. In addition, our results are consistent with a requirement for the DNA induction function in focus formation.
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PMID:The amino-terminal region of the adenovirus serotype 5 E1a protein performs two separate functions when expressed in primary baby rat kidney cells. 297 54

Few human cell systems have been described in which a number of different genes induce transformation. The present investigation reports on our studies using primary human embryo retinoblasts as a model system to monitor transformation and the subsequent behaviour of individual transformants in terms of establishment, the frequency of immortalization and tumourigenic potential. SV40, Adenovirus E1 and E1A, and combinations of Adenovirus E1A and activated H-ras or N-ras were examined as transforming agents. Considerable differences were observed in the ability of these genes to transform human cells, to induce immortal lines and to produce cell lines with a tumourigenic phenotype. Activated ras genes were non-transforming in this system and the degree of complementation with adenovirus E1As in transformation experiments was dependent on both the adenovirus serotype and the ras gene used. The development of tumourigenic cell lines required the expression of more than one oncogene and additional genetic events were required in some in some instances before immortal cell lines were obtained. These findings contribute to the concept that the development of cancer is a multi-step process.
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PMID:Transformation of human embryo retinoblasts with simian virus 40, adenovirus and ras oncogenes. 301 83

The cellular responses to ras and nuclear oncogenes were investigated in purified populations of rat Schwann cells. v-Ha-ras and SV40 large T cooperate to transform Schwann cells, inducing growth in soft agar and allowing proliferation in the absence of added mitogens. Expression of large T alone reduces their growth factor requirements but is insufficient to induce full transformation. In contrast, expression of v-Ha-ras leads to proliferation arrest in Schwann cells expressing a temperature-sensitive mutant of large T at the restrictive temperature. Cells arrest in either the G1 or G2/M phases of the cell cycle, and can re-enter cell division at the permissive temperature even after prolonged periods at the restrictive conditions. Oncogenic ras proteins also inhibit DNA synthesis when microinjected into Schwann cells. Adenovirus E1a and c-myc oncogenes behave similarly to SV40 large T. They cooperate with Ha-ras oncogenes to transform Schwann cells, and prevent ras-induced growth arrest. Thus nuclear oncogenes fundamentally alter the response of Schwann cells to a ras oncogene from cell cycle arrest to transformation.
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PMID:Ras-mediated cell cycle arrest is altered by nuclear oncogenes to induce Schwann cell transformation. 304 71

Adenovirus E1A proteins can transform primary cells in culture in conjunction with other oncogenes, such as E1B or activated ras. The modulation of various cell cycle regulators by E1A is thought to be involved in this transformation process. In this paper we show that E1A enhances the expression of the mitogen-inducible p70 S6 kinase (p70s6k), a kinase which is essential for G1 progression. p70s6k mRNA and protein levels are enhanced 3-4-fold in various E1A-expressing cell lines. Similarly, the activity of p70s6k is enhanced in E1A-expressing cells in a manner partially independent of enhanced expression of p70s6k. The induction of p70s6k correlates with the presence of conserved region 1 (CR1) of E1A and with morphological transformation by E1A. These results suggest that induction of p70s6k by E1A might be involved in transformation by E1A.
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PMID:Induction of the mitogen-activated p70 S6 kinase by adenovirus E1A. 784 79

The PC Cl 3 cell line is a well characterized epithelial thyroid cell line of Fischer rat origin. This cell line has the peculiarity of retaining in vitro the typical markers of thyroid differentiation (i.e. thyroglobulin synthesis and secretion, iodide uptake and dependence on TSH for growth). The PC Cl 3 cells have been transfected with the E1A gene of Adenovirus 5. The E1A transfected cells, PC E1A, partially lost the dependency on TSH for growth and completely lost the ability to trap iodide and synthesize thyroglobulin; however they did not acquire the typical markers of the neoplastic phenotype. A highly malignant phenotype was achieved after infection of the PC E1A cells with retroviruses carrying the v-raf, v-abl and polyoma virus middle T oncogenes. In contrast, the PC E1A cells transfected with the E1B gene of Adenovirus were not tumorigenic at all, and those infected with retroviruses carrying oncogenes of the ras family displayed a very weak tumorigenic phenotype.
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PMID:The Adenovirus E1A gene blocks the differentiation of a thyroid epithelial cell line, however the neoplastic phenotype is achieved only after cooperation with other oncogenes. 842 35


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