Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors

Levanon, Ditsa; Goldstein, Robert E.; Bernstein, Yael; Tang, Hua; Goldenberg, Dalia; Stifani, Stefano; Paroush, Ze’ev; Groner, Yoram

doi:10.1073/pnas.95.20.11590

Cited by 427 publications

(361 citation statements)

References 47 publications

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“…Furthermore, we have preliminary data to support the idea that Grg5 is a coactivator of the transcription factor Cbfa1/Runx2. Grg5 is also reported to interact with Aml1/Cbfa2/Runx1 and modulate its transcriptional activity in vitro (Imai et al, 1998;Levanon et al, 1998;Lutterbach et al, 2000;McLarren et al, 2000). We suggest that Grg5 regulates Cbfa1/Runx2 in the growth plate and that this regulation in turn controls Ihh signaling.…”

Section: Discussionmentioning

confidence: 68%

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Wang

Plotkina

et al. 2002

Developmental Dynamics

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Gene-targeted disruption of Grg5, a mouse homologue of Drosophila groucho (gro), results in postnatal growth retardation in mice. The growth defect, most striking in approximately half of the Grg5 null mice, occurs during the first 4 -5 weeks of age, but most mice recover retarded growth later. We used the nonlinear mixed-effects model to fit the growth data of wild-type, heterozygous, and Grg5 null mice. On the basis of preliminary evidence suggesting an interaction between Grg5 and the transcription factor Cbfa1/Runx2, critical for skeletal development, we further investigated the skeleton in the mice. A long bone growth plate defect was identified, which included shorter zones of proliferative and hypertrophic chondrocytes and decreased trabecular bone formation. This decreased trabecular bone formation is likely caused by a reduced recruitment of osteoblasts into the growth plate region of Grg5 null mice. Like the growth defect, the growth plate and trabecular bone abnormality improved as the mice grew older. The growth plate defect was associated with reduced Indian hedgehog expression and signaling. We suggest that Grg5, a transcriptional coregulator, modulates the activities of transcription factors, such as Cbfa1/Runx2 in vivo to affect Ihh expression and the function of long bone growth plates.

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Section: Discussionmentioning

confidence: 68%

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Wang

Plotkina

et al. 2002

Developmental Dynamics

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“…Cofactors that modulate Tcf activity may also influence the effects of butyrate in HCT-116 cells. Overexpression of TLE1, a corepressor of Tcf in mammalian cells, 49 abrogated the upregulation of expression from the matrilysin promoter (p Ͻ 0.01) in butyratetreated HCT-116 cells (data not shown). However, the role of TLE in modulating Tcf4-dependent Wnt activity is controversial.…”

Section: Discussionmentioning

confidence: 92%

Cell type‐ and promoter‐dependent modulation of the Wnt signaling pathway by sodium butyrate

Bordonaro

Lazarova

Augenlicht

et al. 2001

Intl Journal of Cancer

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The Wnt signaling pathway modulates the transcription of genes linked to proliferation, differentiation and tumor progression. ␤-Catenin-Tcf (BCT)-dependent Wnt signaling is influenced by the short-chain fatty acid sodium butyrate, which induces growth arrest and/or maturation of colonic carcinoma cells. We have compared the effects of sodium butyrate on BCT-dependent signaling in 2 colon carcinoma cell lines that differ in their physiologic response to butyrate, with SW620 cells responding to butyrate by undergoing terminal differentiation and apoptosis, and HCT-116 cells undergoing reversible growth arrest, but no significant apoptotic cell death. Furthermore, these colon carcinoma cell lines differ in their mechanism of Wnt pathway activation, with adenomatous polyposis coli (APC) mutant SW620 cells having high levels of BCT complexes and APC wild-type HCT-116 cells having mutant ␤-catenin, low levels of BCT complexes and correspondingly higher levels of free Tcf. We have demonstrated that in SW620 cells, butyrate downregulates BCT-dependent expression of the Tcf-TK, matrilysin and cyclin D1 promoters, whereas in HCT-116 cells, butyrate upregulates expression of these promoters. Cotransfection with expression vectors that interfere with the Wnt pathway suggests that butyrate enhances BCT complex-DNA binding. Butyrate reduces the expression of Tcf4 in HCT-116 cells, consistent with the induction by butyrate of Tcf-repressible promoters in these cells. These findings indicate that sodium butyrate modulates the Wnt pathway in SW620 and HCT-116 cells in a different manner and that these differences have consequences for promoter activity that may influence the physiologic response to butyrate.

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“…have been identified. 21,[56][57][58] Also, a synergy between b-catenin-TCF/LEF complexes and other transcription factors (including AP-1 or PEA-3) have been described in the promoter regulation of several b-catenin/TCF targets genes including MMP-7 or the g2 chain of laminin-5. 35,59 The human MCP-1 promoter has accordingly been shown to be activated by several transcription factors including NFjB, Sp1 or AP-1.…”

Section: Discussionmentioning

confidence: 99%

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Mestdagt

Polette

Butticè

et al. 2005

Intl Journal of Cancer

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The loss of E-cadherin expression and the translocation of b-catenin to the nucleus are frequently associated with the metastatic conversion of epithelial cells. In the nucleus, b-catenin binds to the TCF/LEF-1 (T-cell factor/ lymphoid enhancer factor) transcription factor family resulting in the activation of several genes, some of them having important implications in tumour progression. In our study, we investigated the potential regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) expression by the b-catenin/TCF pathway. This CC-chemokine has been implicated in tumour progression events such as angiogenesis or tumour associated macrophage (TAM) infiltration. We thus demonstrated that MCP-1 expression correlates with the reorganization of the E-cadherin/b-catenin complexes. Indeed, MCP-1 was expressed by invasive breast cancer cells (MDA-MB-231, BT549 and Hs578T), which do not express E-cadherin but was not produced by noninvasive breast cancer cell lines (MCF7 and T47D) expressing high level of E-cadherin. In addition, the MCP-1 promoter was activated in BT549 breast cancer cells transfected with b-catenin and TCF-4 cDNAs. The MCP-1 mRNA level was similarly upregulated. Moreover, we showed that MCP-1 mRNA was downregulated after transfection with a siRNA against b-catenin in both BT549 and Hs578T cells. Our results therefore identify MCP-1 as a target of the b-catenin/TCF/LEF pathway in breast tumour cells, a regulation which could play a key role in breast tumour progression. ' 2005 Wiley-Liss, Inc.Key words: MCP-1; b-catenin; breast cancer Chemokines constitute a superfamily of proinflammatory cytokines that are implicated in tumour progression, modulating not only host tumour-specific immunological response but also angiogenesis or tumour cell invasion and proliferation. 1-3 Monocyte chemotactic protein-1 (MCP-1) or CCL2 is a CC-chemokine that specifically attracts monocytes and memory T cells. It has been particularly implicated in processes characterized by mononuclear cell infiltration including breast cancer. 4,5 In some models, MCP-1 has been shown to display an antitumoral effect. 6,7 Nevertheless, a large number of studies demonstrate that MCP-1 facilitates tumour progression through its ability to recruit stromal cells including tumour associated macrophages (TAMs) and endothelial cells. 7-10 A pro-angiogenic role of MCP-1 has been demonstrated in many systems, facilitating tumour growth and dissemination. 8,9,11,12 Moreover, a direct effect of MCP-1 on tumour cell migration in vitro has also been described. 13 Recently, Lebrecht et al. 14 have correlated an increased MCP-1 serum level with an advanced breast tumour stage and the presence of lymph node metastasis. In the same way, Amann et al. 15 reported a significant association between MCP-1 urinary levels and tumour stage and grade. They suggested a use of its urinary level as prognosis marker in bladder cancer. The correlation between MCP-1 expression and a poor prognosis was also demonstrated for the squamous cell carcinoma of the oeso...

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Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors

Cited by 427 publications

References 47 publications

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Cell type‐ and promoter‐dependent modulation of the Wnt signaling pathway by sodium butyrate

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

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