Epigenetic regulation of ID4 in breast cancer: Tumor suppressor or oncogene?
| Autor: | Guillermo Urrutia, María Roqué, Maria Teresita Branham, Emanuel M. Campoy, Sergio Laurito, Daniela Nasif, Richard Branham |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Estrogen receptor lcsh:Medicine medicine.disease_cause Epigenesis Genetic 0302 clinical medicine Breast cancer Cell Movement Genetics (clinical) METHYLATION Tumor suppressor purl.org/becyt/ford/3.1 [https] Bioquímica y Biología Molecular Prognosis Gene Expression Regulation Neoplastic Medicina Básica Receptors Estrogen 030220 oncology & carcinogenesis MCF-7 Cells Female purl.org/becyt/ford/3 [https] Signal Transduction medicine.drug CIENCIAS MÉDICAS Y DE LA SALUD Tumor suppressor gene lcsh:QH426-470 Down-Regulation Breast Neoplasms Biology Methylation 03 medical and health sciences BREAST CANCER Cell Line Tumor Genetics medicine Humans Epigenetics Molecular Biology Oncogene Fulvestrant Research lcsh:R DNA Methylation medicine.disease Survival Analysis lcsh:Genetics 030104 developmental biology ID4 Cancer research Inhibitor of Differentiation Proteins Ectopic expression TUMOR SUPPRESSOR Carcinogenesis Developmental Biology |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Clinical Epigenetics, Vol 10, Iss 1, Pp 1-14 (2018) Clinical Epigenetics |
| DOI: | 10.1186/s13148-018-0542-8 |
| Popis: | Background: Inhibitor of differentiation protein 4 (ID4) is a dominant negative regulator of the basic helix-loop-helix (bHLH) family of transcription factors. During tumorigenesis, ID4 may act as a tumor suppressor or as an oncogene in different tumor types. However, the role of ID4 in breast cancer is not clear where both an oncogenic and a tumor suppressor function have been attributed. Here, we hypothesize that ID4 behaves as both, but its role in breast differs according to the estrogen receptor (ER) status of the tumor. Methods: ID4 expression was retrieved from TCGA database using UCSC Xena. Association between overall survival (OS) and ID4 was assessed using Kaplan-Meier plotter. Correlation between methylation and expression was analyzed using the MEXPRESS tool. In vitro experiments involved ectopic expression of ID4 in MCF-7, T47D, and MDA-MB231 breast cancer cell lines. Migration and colony formation capacity were assessed after transfection treatments. Gene expression was analyzed by ddPCR and methylation by MSP, MS-MLPA, or ddMSP. Results: Data mining analysis revealed that ID4 expression is significantly lower in ER+ tumors with respect to ER- tumors or normal tissue. We also demonstrate that ID4 is significantly methylated in ER+ tumors. Kaplan-Meier analysis indicated that low ID4 expression levels were associated with poor overall survival in patients with ER+ tumors. In silico expression analysis indicated that ID4 was associated with the expression of key genes of the ER pathway only in ER+ tumors. In vitro experiments revealed that ID4 overexpression in ER+ cell lines resulted in decreased migration capacity and reduced number of colonies. ID4 overexpression induced a reduction in ER levels in ER+ cell lines, while estrogen deprivation with fulvestrant did not induce changes neither in ID4 methylation nor in ID4 expression. Conclusions: We propose that ID4 is frequently silenced by promoter methylation in ER+ breast cancers and functions as a tumor suppressor gene in these tumors, probably due to its interaction with key genes of the ER pathway. Our present study contributes to the knowledge of the role of ID4 in breast cancer. Fil: Nasif, Daniela Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo; Argentina Fil: Campoy, Emanuel Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo; Argentina Fil: Laurito, Sergio Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo; Argentina Fil: Branham, Richard Lacy. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Urrutia, Guillermo Alejandro. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo; Argentina Fil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo; Argentina Fil: Branham, Maria Teresita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo; Argentina |
| Databáze: | OpenAIRE |
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