title: SV40 infection induces telomerase activity in human mesothelial cells.
abstract: Mesotheliomas are malignant tumors of the pleural and peritoneal membranes which are often associated with asbestos exposure and with Simian virus 40 (SV40) infection. Telomerase activity is repressed in somatic cells and tissues but is activated in immortal and malignant cells. We evaluated telomerase activity in seven primary malignant mesothelioma biopsies and matched lung specimens and 20 mesothelioma cell lines and eight corresponding primary tumor cultures. All the tumor biopsies, and nearly all primary cell mesothelioma cultures and cell lines were telomerase positive. The findings in cell lines paralleled those observed in primary cultures in cases where paired samples were available. Next, we found that SV40, a DNA tumor virus present in approximately 50% of mesothelioma biopsies in the USA, induced telomerase activity in primary human mesothelial cells, but not in primary fibroblasts. Telomerase activity became detectable as early as 72 h following wild-type (strain 776) SV40 infection, and a clear DNA ladder was detectable 1 week after infection. The amount of telomerase activity increased during passage in cell culture and appeared to parallel increases in the cellular amounts of the SV40 large T-antigen. Thus, SV40 infection leads to telomerase activity before the infected mesothelial cells become transformed and immortalized. SV40 infection of human fibroblasts did not cause detectable telomerase activity. We also determined that the SV40 small t-antigen (tag) plays an important role in inducing telomerase activity because this activity was undetectable or minimal in mesothelial cells infected and/or transformed by SV40 tag mutants. Asbestos alone did not induce telomerase activity, and asbestos did not influence telomerase activity in mesothelial cells infected with SV40. Induction of telomerase activity by SV40 may be related to the very high rate of mesothelial cell immortalization that is characteristically associated with SV40 infection of mesothelial cells.
authors.affiliation: Cancer Immunology Program, Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois, IL 60153, USA.
authors.forename: Rudy
authors.initials: R
authors.lastname: Foddis
authors.forename: Assunta
authors.initials: A
authors.lastname: De Rienzo
authors.forename: Dominique
authors.initials: D
authors.lastname: Broccoli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bocchetta
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stekala
authors.forename: Paola
authors.initials: P
authors.lastname: Rizzo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tosolini
authors.forename: Jennifer V
authors.initials: JV
authors.lastname: Grobelny
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Jhanwar
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
authors.forename: Michele
authors.initials: M
authors.lastname: Carbone
mesh_terms: D015139:Blotting, Southern; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004790:Enzyme Induction; D004848:Epithelium / Q000201:enzymology / Q000473:pathology / Q000821:virology; D017353:Gene Deletion; D006801:Humans; D008654:Mesothelioma / Q000201:enzymology* / Q000821:virology*; D013539:Simian virus 40 / Q000502:physiology*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D019098:Telomerase