title: Cultured human atherosclerotic plaque smooth muscle cells retain transforming potential and display enhanced expression of the myc protooncogene.
abstract: The proliferation of vascular smooth muscle cells (SMC) is critical to atherosclerotic plaque formation. The monoclonal hypothesis proposes that the stimulus for this SMC proliferation is a mutational event. Here we describe a procedure for growing human plaque smooth muscle cells (p-SMC) in culture. We show that p-SMCs derived from two patients differ from SMC cultured from normal vascular tissue in expression of the protooncogene myc. One p-SMC strain was extensively characterized; these diploid, karyotypically normal cells have a finite life span in culture. Ultrastructural examination revealed two populations, one with classic contractile SMC appearance, the other, modulated to a synthetic state. Northern blotting showed a 2- to 6-fold and a 6- to 11-fold enhanced expression of myc by p-SMC, compared to SMC derived from healthy human aorta (HA-SMC) and saphenous vein (HV-SMC), respectively. In contrast, the p-SMC and HV-SMC expressed similar levels of message for the genes N-myc, L-myc, Ha-ras, fos, sis, myb, LDL receptor, EGF receptor, IGF I receptor, IGF II, and HMG CoA reductase. Finally, although p-SMCs are not tumorigenic, DNA isolated from these cells is positive in the transfection-nude mouse tumor assay. Myc, however, does not appear to be the transforming gene because no newly introduced human myc gene was detected in the p-SMC-associated nude mouse tumor. Thus human atherosclerotic p-SMCs possess both an activated myc gene and a transforming gene that is retained throughout many cell passages.
authors.affiliation: Institute of Environmental Medicine, New York University Medical Center, New York 10016.
authors.forename: J L
authors.initials: JL
authors.lastname: Parkes
authors.forename: R R
authors.initials: RR
authors.lastname: Cardell
authors.forename: F C
authors.initials: FC
authors.lastname: Hubbard
authors.forename: D
authors.initials: D
authors.lastname: Hubbard
authors.forename: A
authors.initials: A
authors.lastname: Meltzer
authors.forename: A
authors.initials: A
authors.lastname: Penn
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009857:Oncogenes; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D014162:Transfection
chemical_list: D016271:Proto-Oncogene Proteins c-myc