Role of adenovirus types 5 and 12 early region 1 b tumor antigens in oncogenic transformation

Recently we have reported that the difference in oncogenic potential between adenovirus type 5 (Ad5)- and Ad12-transformed cells in athymic nude mice is specified by early region 1b. In order to determine which of the two early region 1b. (Elb) tumor antigens is responsible for the observed difference in oncogenicity we have constructed two Ad5/Ad12 hybrid plasmids: one allowing expression of the Ad5 19kD and Ad12 54kD Elb proteins, the other of the Ad5 58kD plus Ad12 19kD Elb polypeptides. Both hybrid plasmids contain the intact Ela regions of both serotypes. The chimeric plasmids were used to transform primary cultures of baby rat kidney cells and the resulting transformed cells were tested for oncogenicity in athymic nude mice. It was found that the degree of oncogenicity is determined by the identity of the large Elb tumor antigen. Studies with cells transformed by an Ad12 region El plasmid in which the gene coding for the 19kD tumor antigen was mutated showed that expression of this protein is nevertheless required for manifestations of the oncogenic phenotype of the transformed cell

Establishment and characterization of an uveal-melanoma cell line

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Characterization of cells transformed by Ad5/Ad12 hybrid early region I plasmids

Early region I (EI) of the human adenoviruses consists of two transcriptional units, EIa and EIb. We have constructed plasmids containing hybrid EI regions from the nononcogenic adenovirus type 5 (Ad5) and the highly oncogenic Ad12. Each plasmid essentially contains the EIa region of one serotype and the EIb region of the other serotype. These hybrid EI plasmids are capable of transforming baby rat kidney cells into cell lines with the typical adenovirus-transformed phenotype, indicating an extensive functional homology between the EI transcriptional units of the two serotypes at the level of transformation. The difference in transformation frequency between the two hybrid EI plasmids suggests that the efficiency of transformation is determined by the identity of the EIa region, i.e., the efficiency is high for clones containing the EIa region of Ad5 and low for clones containing the EIa region of Ad12. In nude mice the Ad5 EIa-Ad12 EIb hybrid-transformed cells show the same high oncogenic potential as Ad12 EI-transformed cells, whereas the Ad12 EIa-Ad5 EIb hybrid-transformed cells express an even lower potential than the Ad5 El-transformed cells, indicating that the difference in oncogenic potential between Ad5- and Ad12-transformed cells is specified by the EIb region

Immunization with interleukin-2 transfected melanoma cells: a phase-I-II study in patients with metastatic melanoma

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Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity

Evidence is presented that cells transformed by adenovirus type 12 are oncogenic because they escape from T cell immunity. This effect is brought about by reducing the expression of class 1 transplantation antigens and is a function of the protein translated from the I3S mRNA, transcibed from early region 1a. These findings establish a novel mechanism by which transformed cells can acquire an oncogenic phenotype

Studies on the role of adenovirus E1 genes in transformation and oncogenesis

Human adenoviruses are divided into at least three subgroups on the basis of their oncogenicity in hamsters: subgroup A containing highly oncogenic viruses, subgroup B weakly oncogenic viruses, and subgroup C (most of the) nononcogenic viruses. Despite these clear distinctions in oncogenic activity among the three sugroups, all human adenoviruses are capable of transforming cultured cells into tumor-like cells

Deletion mutants of region E1 a of AD12 E1 plasmids: Effect on oncogenic transformation

Plasmids containing the El region of Ad12 DNA can transform certain rodent cells into oncogenic cells. To study the role of the Ela subregion in the process of oncogenic transformation, Ad12 region El mutants carrying deletions in the Ela region were constructed. Deletion mutants pR7 and pR8 affect only the 13 S mRNA species encoded by region Ela, whereas deletion mutants pR11 and pR15 damage both the 12 S and 13 S E1a mRNA. All four mutants have lost their capacity to transform primary cultures of baby rat kidney cells, indicating that the Ela gene product encoded by 13 S mRNA is essential for transformation. It was further found that the mutated Ela regions of both pR7 and pR11 can induce expression of region Elb, which implies that the transformation deficiency of these mutants is not due to the inability to activate Elb expression. Surprisingly, the transforming capacity of pR7 and pR11 is restored when these mutant El regions are covalently coupled to the SV40 “enhancer” region. Cells transformed by these hybrids plasmids, however, were not tumorigenic in nude mice

Altered expression of cellular genes in adenovirus-transformed cells

In the present study we report a major contribution of Ad12 region E1A in oncogenicity. We have found that expression of this region in transformed rat cells causes suppression of the production of class-I transplantation antigens and of a 32-kD cellular protein, resulting in a considerable reduction in susceptibility of the transformed cells to the cellular immune defense. This resistence to the host immune defense presumably causes the cells to be tumorigenic, even in immunocompetent animals

Analysis of N-ras mutations in human cutaneous melanoma: tumor heterogeneity detected by polymerase chain reaction/single-stranded conformation polymorphism analysis

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Dail Eireann debate. Priority question 50 - Substance misuse [Awareness campaigns] [32627/07].

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