PubMed · 4064015
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M Calvin. 1985. Evolution and cancer.. https://pubmed.ncbi.nlm.nih.gov/4064015/
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We have constructed an E1-defective adenovirus (Ad) vector designated AdCAG-Cre containing the Cre recombinase gene derived from bacteriophage P1 under control of the cytomegalovirus immediate early enhancer-chicken beta-actin hybrid (CAG) promoter. We examined the Cre-loxP-based recombination by this Ad vector in C2C12 cells bearing a reporter gene construct CAG-CAT-Z, which directs expression of the E. coli lacZ gene upon Cre-mediated excision of the CAT gene located between the CAG promoter and the lacZ gene. Nearly 100% of these cells were shown to start to produce beta-galactosidase after infection with the AdCAG-Cre vector at MOI 100. On the basis of this result, we discuss the possible use of the AdCAG-Cre vector to manipulate the gene expression in mammalian cells.
Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. To determine the role of these proteins in maintaining cancer cell viability, an adenovirus vector that expresses bcl-xs, a functional inhibitor of these proteins, was constructed. Even in the absence of an exogenous apoptotic signal such as x-irradiation, this virus specifically and efficiently kills carcinoma cells arising from multiple organs including breast, colon, stomach, and neuroblasts. In contrast, normal hematopoietic progenitor cells and primitive cells capable of repopulating severe combined immunodeficient mice were refractory to killing by the bcl-xs adenovirus. These results suggest that Bcl-2 family members are required for survival of cancer cells derived from solid tissues. The bcl-xs adenovirus vector may prove useful in killing cancer cells contaminating the bone marrow of patients undergoing autologous bone marrow transplantation.
The fiber and hexon genes of the immunological adenovirus (Ad) variant strains Ad9/Hx and Ad15/Hx, belonging to subgenus D, were sequenced and compared to the corresponding sequences of the prototypes Ad9 and Ad15. It was found that the variants possessed a novel and identical hemagglutinin as they could not be distinguished by hemagglutination-inhibition tests. These serological data were now confirmed on DNA and protein level. The analyzed hexon regions of Ad15 and Ad15/Hx, and Ad9 and Ad9/Hx, respectively, were 100% identical on the amino acid level. The comparison between the variant fibers revealed that they possessed an identical fiber, which was distinct from the Ad9 and Ad15 fiber polypeptides. It seems likely that the donor of the novel fiber protein was a so far unidentified subgroup D adenovirus. The fiber polypeptides of Ad9 and the variants revealed the highest homology (73.7%), whereas the variants and the Ad15 fiber had only 64.2% of the amino acids in common. Most of the differences between the adenovirus serotypes were detected in the fiber knob. Seven conserved sequences found for subgenus D fibers could be confirmed for the fibers of the variants. Furthermore, the data presented complement the knowledge on the organization of subgenus D fiber genes.