p21Waf1 is required for complete oncogenic transformation of mouse embryo fibroblasts by E1Aad5 and c-Ha-ras oncogenes |
| |
Authors: | Romanov Vasily S Bardin Alexander A Zubova Svetlana G Bykova Tatiana V Pospelov Valery A Pospelova Tatiana V |
| |
Affiliation: | a Institute of Cytology, Russian Academy of Sciences, Tikhoretsky Avenue 4, 194064 St. Petersburg, Russia b Department of Cytology and Histology, Faculty of Biology and Soil Sciences, St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia |
| |
Abstract: | Cyclin-dependent kinase inhibitor p21Waf1 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 p21Waf1 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 p21Waf1-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 p21Waf1 “tumor suppressor” having alternative oncogenic functions in the cytoplasm and for the first time indicate that p21Waf1 can be indispensable for complete oncogenic transformation. |
| |
Keywords: | p21Waf1 Oncogenic transformation E1A Ras |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|