| created | [InstanceEdit:9794226] Orlic-Milacic, Marija, 2022-06-29 |
| dbId | 9794228 |
| displayName | Direct upregulation of the CDH1 gene transcription by the re... |
| literatureReference |
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| modified | [InstanceEdit:9936171] Orlic-Milacic, Marija, 2025-01-21 |
| schemaClass | Summation |
| text | Direct upregulation of the CDH1 gene transcription by the retinoblastoma tumor suppressor protein RB1 and the transcription factor TFAP2A was demonstrated in several studies, some of which also showed that RB1 and TFAP2A form a complex at the CDH1 gene promoter. Re-expression of the transcription factor TFAP2A in TFAP2A-negative human colon cancer cell line SW480 results in upregulation of E-cadherin (CDH1) levels, which requires direct binding of TFAP2A to the CDH1 gene promoter (Schwartz et al. 2007). Depletion of RB1 tumor suppressor in human RB1-positive breast cancer cell line MCF7 disrupts cell-cell adhesion and induces epithelial-to-mesenchymal transition (EMT) (Arima et al. 2008). In MCF7 cells, RB1 binds to the CDH1 gene promoter in association with TFAP2A and activates CDH1 gene transcription (Decary et al. 2002; Arima et al. 2008). RB1 and TFAP2A co-immunoprecipitate with the promoter of the CDH1 gene in Madin-Darby canine kidney cell line (MDCK) and immortalized human keratinocytes (HaCat cell line) to activate CDH1 gene transcription (Batsche et al. 1998). TFAP2A directly binds to the mouse Cdh1 gene promoter and upregulates Cdh1 gene transcription in mouse epidermal keratinocytes (Faraldo et al. 1997). TFAP2A-mediated upregulation of the CDH1 gene transcription occurs downstream of the MYC oncogene (Batsche and Cremisi 1999). Proper regulation of CDH1 gene expression by TFAP2A is important for differentiation of mouse lens fiber cells and eye development (West-Mays et al. 2002). |
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