title: Transformation of rabbit vascular smooth muscle cells by human cytomegalovirus morphological transforming region I.
abstract: The association of human cytomegalovirus with atherosclerosis and the monoclonal hypothesis of atherogenesis suggested that transformation of vascular smooth muscle cells may be an outcome of the virus-host cell interaction. To test this hypothesis, rabbit aorta smooth muscle cells were transfected with the morphological transforming region I (mtrI) of human cytomegalovirus (HCMV) linked to the neomycin resistance gene. Foci of neomycin-resistant and morphologically transformed cells were isolated and expanded into fourteen RCMV strains. Eight of these strains acquired immortalization, but only one strain (RCMV-21) retained recombined viral sequences integrated in the cellular DNA. RCMV strains were heterogeneous in their morphology, expression of smooth muscle alpha-actin, growth, and mitogenic response to serum and fibroblast growth factor (FGF)-2 and -4. All RCMV strains assayed except RCMV-3 showed DNA synthesis in low serum medium and, with the exception of RCMV-1 cells, all showed a significant mitogenic response to FGF-2 and FGF-4, Maintenance of the transformed phenotype appeared independent of the retention of the transforming viral sequences, which was suggestive of a "hit-and-run" mechanism. These results suggested that morphological transformation by HCMV DNA sequences could enhance the mitogenic response of vascular smooth muscle cells to fibroblast growth factors.
authors.affiliation: Department of Biochemistry, University of Orléans, France.
authors.forename: A
authors.initials: A
authors.lastname: Legrand
authors.forename: E P
authors.initials: EP
authors.lastname: Mayer
authors.forename: S S
authors.initials: SS
authors.lastname: Dalvi
authors.forename: M
authors.initials: M
authors.lastname: Nachtigal
mesh_terms: D000818:Animals; D001483:Base Sequence; D001790:Blood Physiological Phenomena; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003587:Cytomegalovirus / Q000235:genetics* / Q000502:physiology* / Q000648:ultrastructure; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000821:virology*; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D011817:Rabbits; D013936:Thymidine / Q000378:metabolism
chemical_list: D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D013936:Thymidine