Disruption of scaffold attachment factor B1 leads to TBX2 up-regulation, lack of p19ARF induction, lack of senescence, and cell immortalization.
Scaffold attachment factor B1 (SAFB1) is a multifunctional protein, which has previously been implicated in breast cancer. Here, we show that genetic deletion of SAFB1 in mouse embryonic fibroblasts (MEF) leads to spontaneous immortalization and altered expression of two proteins involved in immortalization and escape from senescence: low levels of p19(ARF) and high levels of TBX2. Inactivation of TBX2 using a dominant-negative TBX2 resulted in up-regulation of p19(ARF) in SAFB1 knockout MEFs. SAFB1 loss also caused lack of contact inhibition, increased foci formation, and increased oncogene-induced anchorage-independent growth. These findings suggest that SAFB1 is a novel player in cellular immortalization and transformation.
Dobrzycka
Klaudia M
KM
Department of Medicine, The Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Kang
Kaiyan
K
Jiang
Shiming
S
Meyer
Rene
R
Rao
Pulivarthi H
PH
Lee
Adrian V
AV
Oesterreich
Steffi
S
D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics*
C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C500609:scaffold attachment factor B1, mouse; D012313:RNA