Id-1 regulates Bcl-2 and Bax expression through p53 and NF-κB in MCF-7 breast cancer cells

Kim, Hwan; Chung, Hyun Kee; Kim, Hyun-Jun; Lee, Jeong-Yeon; Oh, Mi-Yun; Kim, Yong-Seok; Kong, Gu

doi:10.1007/s10549-007-9871-6

Cited by 61 publications

(45 citation statements)

References 46 publications

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“…Id-1 seems to regulate many biological effects by p53 modulation. Recently, we showed that Id-1 regulates both bcl-2 and bax expressions through inhibition of p53 expression and has a protective effect on taxol-induced apoptosis (Kim et al, 2007a). Here, we also demonstrate that Id-1 inhibited PTEN expression and activated the Akt pathway through p53 regulation.…”

Section: Discussionsupporting

confidence: 62%

“…In human breast epithelial cells, Id-1 enhances cyclin D1 and cyclin E expressions and affects CDK4 and CDK2 activities (Swarbrick et al, 2005). We have previously reported the enhancement of cell growth and induction of G 1 to S phase transition by ectopic Id-1 expression in MCF7 breast cancer cells (Kim et al, 2007a). In this study, our data show that Id-1 enhances the Akt-mediated Wnt/TCF pathway and cyclin D1 expression, a TCF/LEF response gene, and leads to Akt-mediated p27 Kip1 phosphorylation and its cytosolic retention in MCF7 breast cancer cells.…”

Section: Discussionmentioning

confidence: 98%

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Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

et al. 2008

Oncogene

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Inhibitor of differentiation-1 (Id-1) has been accepted as a putative oncogene to promote oncogenic processes through inactivation of tumor suppressors and activation of growth promoting pathways. Here, we show that Id-1 activates the Akt pathway by inhibition of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) transcription through downregulation of p53. Id-1 negatively regulated both p53 and PTEN at the transcriptional level. In promoter assay with serial deletion and chromatin immunoprecipitation assay, the binding of p53 to the PTEN promoter was reduced by Id-1, suggesting that Id-1 regulates PTEN transcription through its p53 modulation. This led to Akt phosphorylation at Ser473 and the activation of the Akt-mediated canonical Wnt signaling pathway. The glycogen synthase kinase-3b phosphorylation at Ser9, stabilization and nuclear localization of b-catenin, T-cell factor (TCF)/lymphoid enhancer factor transactivation activity and cyclin D1 expression were enhanced by Id-1. On the other hand, Akt-mediated p27 Kip1 phosphorylation at Thr157 and its cytosolic localization were also increased in Id-1 overexpressing MCF7 cells. In conclusion, our results disclose Id-1 as a novel PTEN inhibitor that could activate the Akt pathway and its downstream effectors, the Wnt/TCF pathway and p27 Kip1 phosphorylation and suggest that the oncogenic function of Id-1 may be partly attributed to its PTEN inhibition in human breast carcinogenesis.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 98%

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

et al. 2008

Oncogene

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“…Overexpression of Id proteins in embryonic-derived fibroblasts facilitates cell cycle S-phase under serum-deprived conditions [34], where Id-1 has been reported to induce the proliferation of cochlear sensory epithelial cells via the NF-kappaB/cyclin D1 pathway [35]. Furthermore, various cancer cell lines appear to require Id-1 and Id-2 expression for their growth, survival, and metastasis via regulation of p53 and PI3K/Akt/NF-kappaB signaling pathways in a similar fashion to that described for Twist-1 and Dermo-1 [36][37][38][39][40]. More recently, Id-1 has been shown to mediate long-term repopulating hematopoietic stem cell maintenance and inhibit myeloid differentiation [41,42].…”

Section: Discussionmentioning

confidence: 82%

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

et al. 2009

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The TWIST family of basic helix-loop-helix transcription factors, Twist-1 and Dermo-1 are known mediators of mesodermal tissue development and contribute to correct patterning of the skeleton. In this study, we demonstrate that freshly purified human bone marrow-derived mesenchymal stromal/stem cells (MSC) express high levels of Twist-1 and Dermo-1 which are downregulated following ex vivo expansion. Enforced expression of Twist-1 or Dermo-1 in human MSC cultures increased expression of the MSC marker, STRO-1, and the early osteogenic transcription factors, Runx2 and Msx2. Conversely, overexpression of Twist-1 and Dermo-1 was associated with a decrease in the gene expression of osteoblast-associated markers, bone morphogenic protein-2, bone sialoprotein, osteopontin, alkaline phosphatase and osteocalcin. High expressing Twist-1 or Dermo-1 MSC lines exhibited an enhanced proliferative potential of approximately 2.5-fold compared with control MSC populations that were associated with elevated levels of Id-1 and Id-2 gene expression. Functional studies demonstrated that high expressing Twist-1 and Dermo-1 MSC displayed a decreased capacity for osteo/chondrogenic differentiation and an enhanced capacity to undergo adipogenesis. These findings implicate the TWIST gene family members as potential mediators of MSC self-renewal and lineage commitment in postnatal skeletal tissues by exerting their effects on genes involved in the early stages of bone development.

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“…The mechanism by which Id1 regulates the expression of β1-integrin is still not clear. Recently, it was reported that p53 expression may regulate the recycling of β1-integrin (25), and Id1 can regulate the expression of p53 (26). We propose that the interaction of Id1 and p53 is essential for Id1-mediated expression of β1-integrin, a possibility that will be addressed in future study.…”

Section: Discussionmentioning

confidence: 81%

Id1 induces tubulogenesis by regulating endothelial cell adhesion and cytoskeletal organization through β1-integrin and Rho-kinase signalling

Qiu

Wang

Qin³

et al. 2011

Int J Mol Med

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Abstract. The inhibitor of differentiation 1 (Id1) protein is required for tubulogenesis, but the molecular signalling pathways remain unclear. Overexpression (Id1-t) or downregulation (si-Id1) of Id-1 in cell lines, were used to study the function of Id1. The expression of Id1 and β1-integrin was assessed by Western blotting. Up-regulation of Id1 in human umbilical vascular endothelial cells (HUVECs) activated the expression of β1-integrin and promoted cell adhesion and spreading. Conversely, down-regulation of Id1 suppressed β1-integrin expression and inhibited tubulogenesis. By using a β1-integrin antibody to inhibit β1-integrin function, we demonstrated that Id1-induced cell adhesion and tubulogenesis were mediated by β1-integrin. In addition, HUVECs overexpressing Id1 were able to promote capillary tube formation through cytoskeleton reorganization and cell contraction. Finally, the Rho-kinase inhibitor Y27632 inhibited tubulogenesis induced by Id1. Our findings provide evidence that Id1 regulates tubulogenesis in vitro through β1-integrin and Rho-kinase signalling. IntroductionControlled angiogenesis is vital for normal organ development and tissue repair, while angiogenesis can sustain tumorigenesis and age-related macular degeneration (1). In addition, angiogenesis is a key event in the pathogenesis of some forms of cardiovascular disease (2). Although angiogenesis has been identified as a key development in many progressive diseases, the specific molecular mechanisms of angiogenesis are not well understood.The four Id (inhibitor of differentiation or DNA binding) proteins (Id1-4) all contain a helix-loop-helix motif that inhibits the activity of basic helix-loop-helix transcription factors by restraining DNA binding. The Id1 protein has been implicated in the regulation of the cell cycle and in differentiation (3). Since the initial discovery that Id1 is required for angiogenesis (4), Id1 protein induced-angiogenesis has been studied in several experimental systems. Transplantation of mature endothelial cells overexpressing Id1 may serve as a novel and useful strategy for therapeutic angiogenesis (5). Studies have also indicated that the overexpression of Id1 protein was correlated with angiogenesis in tumors (6). Although the molecular mechanisms of Id1-mediated cell proliferation and apoptosis have been identified (7), little is known about the mechanism of Id1-mediated angiogenesis.Angiogenesis is a complex event and requires a wellorchestrated integration of migration, proliferation, extracellular matrix (ECM) degradation, cell contraction, and survival. Previous studies reported that Id1 can regulate cell migration (5), proliferation (5) and ECM degradation (8). However, cellmatrix adhesion and F-actin cytoskeleton reorganization, which play crucial roles in endothelial cell adhesion during angiogenesis (9,10), were absent. Moreover, cytoskeletal regulatory molecules are probably involved in angiogenesis (11). Furthermore, angiogenesis requires a polarized morphology with a single, broad lamellipod...

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Id-1 regulates Bcl-2 and Bax expression through p53 and NF-κB in MCF-7 breast cancer cells

Cited by 61 publications

References 46 publications

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

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

Id1 induces tubulogenesis by regulating endothelial cell adhesion and cytoskeletal organization through β1-integrin and Rho-kinase signalling

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