Transformation of rabbit vascular smooth muscle cells by human cytomegalovirus morphological transforming region I.
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.
Legrand
A
A
Department of Biochemistry, University of Orléans, France.
Mayer
E P
EP
Dalvi
S S
SS
Nachtigal
M
M
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
D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D013936:Thymidine