title: [Antiapoptotic gene bcl-2 prevents cellular senescence program reactivation induced by histone deacetylase inhibitor sodium butyrate in E1A and cHa-ras transformed rat fibroblasts].
abstract: We have investigated the role of apoptosis resistance gene bcl-2 in the activation of cellular senescence program induced by histone deacetylase inhibitor (HDACi) sodium butyrate (NaBut) in transformed rat fibroblasts. This study was conducted in a resistant to apoptosis induction cell line of rat embryo fibroblasts transfor- med by oncogenes E1A, cHa-ras and bcl-2 (ERasBcl). The parent cell line transformed with only EJA and cHa-ras (ERas) was used as a control. It has been found that NaBut reduces proliferation rate of ERasBcl cells significantly weaker than of ERas transformed cells, despite the fact that the G1 cell cycle arrest was observed in both cell lines. After NaBut treatment, hypertrophy of the apoptosis resistant transformants ERasBcl also was reduced compared to parent cell line ERas, due to less activation of mTORC1, which is known to control the synthesis of protein and ribosome biogenesis. The degree of mTORC1 activation was as.sessed by its target proteins phosphorylation: the ribosomal S6 protein and 4E-BP1--inhibitor of translation initiation factor eIF4E. Since cell senescence process may be associated with changes in autophagy regulation, we analyzed the dynamics of one of the main autophagosome formation markers--protein LC3. The accumulation of lipid-bound form LC3-II changes significantly in ERasBcl cells after NaBut treatment and has transient nature. The set of analyzed cellular senescence markers suggests that a high level of apoptosis resistance gene bcl-2 expression prevents the realization of tumor-suppressor senescence program induced by HDACi sodium butyrate treatment.
authors.forename: S A
authors.initials: SA
authors.lastname: Gordeev
authors.forename: T V
authors.initials: TV
authors.lastname: Bykova
authors.forename: S G
authors.initials: SG
authors.lastname: Zubova
authors.forename: N D
authors.initials: ND
authors.lastname: Aksenov
authors.forename: T V
authors.initials: TV
authors.lastname: Pospelova
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D020148:Butyric Acid / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D019925:Cyclin A / Q000096:biosynthesis / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D011905:Genes, ras / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats
chemical_list: D019925:Cyclin A; D056572:Histone Deacetylase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D020148:Butyric Acid