TWIST inactivation reduces CBFA1/RUNX2 expression and DNA binding to the osteocalcin promoter in osteoblasts

Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells

“…As shown in Figure 3, decreased p53, p21 Waf1 but not MDM2 was found in the subline HNE1-T3 cells compared to the parental line HNE1, while downregulation of Bax, an factor, was observed pre-apoptotic in HNE1-T3 cells. These results also agree with previous reports that TWIST suppresses expression of p53, p21 Waf1 and Bax leading to decreased apoptosis in osteoblast cells (Maestro et al, 1999;Yousfi et al, 2002). We are currently investigating the effect of exogenous TWIST expression on p53, p21 Waf1 , Bax and Bcl-2 expression in the stable transfectants generated in the present study to further confirm this hypothesis.…”

“…In addition, we also observed an approximate 90% reduction in Bax levels in HNE1-T3 cells, while there was a slight decrease in Bcl-2 expression (Figure 3c). These results support previous evidence that TWIST expression was associated with decreased Bax but not Bcl-2 levels in osteoblast cells from patients suffering from Saethre-Chotzen syndrome, which is one of the most common autosomal dominant disorders of craniosynostosis (early closing of one or more of the sutures of an infant's head), and TWIST inactivation is thought to be one of the mechanisms responsible (El Ghouzzi et al, 1997;Howard et al, 1997;Yousfi et al, 2002).…”

“…The TWIST protein is a highly conserved transcription factor that belongs to the family of basic helix-loop-helix proteins (Olson and Klein, 1994), which play a central role in cell type determination and differentiation (Olson and Klein, 1994). It has been indicated that TWIST plays a crucial role in cranial osteogenesis, and TWIST haploinsufficiency enhances apoptosis in osteoblasts leading to premature fusion of calvarial bones (craniosynostosis) (Yousfi et al, 2002). Although the function of TWIST is not fully established at the molecular level, recently TWIST has been indicated as a potential oncogene interfering with p53-related pathways leading to preventing myc-induced apoptosis in mouse embryonal fibroblasts (Maestro et al, 1999).…”

“…As shown in Figure 3a, TWIST mRNA and protein expressions were 4.0-and 5.2-fold higher in HNE1-T3 cells as compared to HNE1 cells, respectively, which confirms the CGH results and indicates a TWIST gene amplification in HNE1-T3 cells. Since p53, p21 Waf1 , MDM2, Bax proteins have been reported to be downstream factors of the TWIST protein (Maestro et al, 1999;Funato et al, 2001;Yousfi et al, 2002), we next studied the expression of these proteins in HNE1-T3 and HNE1 cells. As shown in Figure 3b, p53, p21 Waf1 protein levels were low in HNE1-T3 cells, but MDM2 levels were high, which agrees with a previous study that TWIST may negatively interfere with the p53 tumour suppressor pathway (Maestro et al, 1999).…”

TWIST Family of Basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stem Cell Growth and Commitment

“…Previous findings have demonstrated an increase in ALP, OPN, and BSP gene expression following siRNA knockdown of Twist in human periodontal ligament cells [44], and Twist antisense knockdown in osteosarcoma cell lines [11]. Other studies have also reported a reduction in Runx2 expression and activity in TWIST haploinsufficiency mutant osteoblasts [45], and in cancer cell lines, following shRNA knockdown of Twist-1 [46].…”