title: p21Waf1 is required for complete oncogenic transformation of mouse embryo fibroblasts by E1Aad5 and c-Ha-ras oncogenes.
abstract: Cyclin-dependent kinase inhibitor p21(Waf1) is known to have alternative functions associated with positive regulation of proliferation, actin cytoskeleton remodeling and suppression of apoptosis. The goal of the present study was to assess the role of p21(Waf1) in the establishment of the transformed phenotype of mouse embryo fibroblasts with stable expression of E1Aad5 and c-Ha-ras complementary oncogenes. Herein, we demonstrate that E1A/c-Ha-Ras-transformed p21(Waf1)-null fibroblasts possess some characteristic features of transformed cells, such as loss of contact inhibition, high saturation density, shortened cell cycle, inability to undergo cell-cycle arrest after DNA damage and serum deprivation, but, at the same time, they are not completely transformed in that they are unable to proliferate at clonal density, are anchorage-dependent, retain a fibroblast-like morphology with pronounced actin cytoskeleton and show reduced migration and invasion. Our data support the concept of p21(Waf1) "tumor suppressor" having alternative oncogenic functions in the cytoplasm and for the first time indicate that p21(Waf1) can be indispensable for complete oncogenic transformation.
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, Tikhoretsky Avenue 4, 194064 St. Petersburg, Russia. vsromanov@hotmail.com
authors.forename: Vasily S
authors.initials: VS
authors.lastname: Romanov
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Bardin
authors.forename: Svetlana G
authors.initials: SG
authors.lastname: Zubova
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Bykova
authors.forename: Valery A
authors.initials: VA
authors.lastname: Pospelov
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Pospelova
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002461:Cell Line, Transformed; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D011905:Genes, ras; D051379:Mice; D009857:Oncogenes; D014161:Transduction, Genetic
chemical_list: D017500:Adenovirus E1A Proteins; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21