Estudio de la regulación epigenética de ID4 en cáncer de mama
Breast cancer is the leading cause of death in women in both developed and developing countries. From the biological point of view, it is an heterogeneous disease that includes a set of biologically different entities. Molecularly, breast tumors are classified into five groups: two groups that expre...
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2019
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| Acceso en línea: | https://bdigital.uncu.edu.ar/fichas.php?idobjeto=14714 |
| date_str_mv |
2019-2021 |
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| todos_str_mv |
80020180100949UN Estudio de la regulación epigenética de ID4 en cáncer de mama Proyecto de investigación siip2019-2021 UNCuyo FCM UNCuyo FCM I. de Histología y Embriología |
| autor_str_mv |
Branham, María Teresita Lurito, Sergio Roberto Nasif, Daniela Lucía Roqué Moreno, María |
| description_str_mv |
Breast cancer is the leading cause of death in women in both developed and developing countries. From the biological point of view, it is an heterogeneous disease that includes a set of biologically different entities. Molecularly, breast tumors are classified into five groups: two groups that express estrogen receptor (ER), which include tumors of type Luminal A (ER + and Her2-) and type Luminal B (ER + and Her2 +) and three groups that do not express estrogen receptor (ER-), and include Her2 tumors, "normal like" and "basal like" tumors whose majority are triple negative (TN). During the mammary tumorigenic process, both genetic and epigenetic alterations accumulate. Unlike genetic sequences, which are usually highly conserved, epigenetic modifications reveal a different dynamism. During the tumorigenic processes these modifications are deregulated, generating global genomic hypomethylation and hypermethylation in regulatory regions of the genome. ID (inhibitor of DNA binding) proteins are transcriptional regulators that control the differentiation of stem cells and progenitor cells during development and adult life. To date, 4 members of this family have been described: ID1, ID2, ID3 and ID4. For ID4 it has been postulated that it has a tumor suppressive role in some tumor types such as bladder, colon and leukemias; but its role in mammary tumors is controversial where both suppressive and oncogenic functions have been described. Data mining analysis of TCGA (The Cancer Genome Atlas) reveal that the expression of ID4 is high in normal mammary tissue and mammary tumors of the TN subtype (RE-), while its expression is reduced in luminal tumors A and luminal B tumors (RE +). That is to say that ID4 seems to have a dual role depending on the cellular context. Given that, to date, no mutations for ID4 have been characterized and that the main mechanism for gene regulation is through promoter methylation, we hypothesize that: there is a differential epigenetic regulation of ID4 in TN and non-TN mammary tumors. To test our hypothesis we propose: a) -Determine if estrogen levels mediate ID4 methylation in mammary tumors; b) -Evaluate whether EZH2 participates in the methylation of ID4 in mammary tumors. We consider that our project will contribute to the knowledge of the epigenetic regulation of ID4 in mammary carcinogenesis. El cáncer de mama es la primera causa de muerte en mujeres tanto en países desarrollados como en países en vía de desarrollo. Desde el punto de vista biológico es una enfermedad heterogénea que incluye un conjunto de entidades biológicamente diferentes. Molecularmente los tumores de mama se clasifican en cinco grupos: dos grupos que expresan receptor de estrógenos (RE), que incluyen a los tumores de tipo Luminal A (RE+ y Her2-) y de tipo Luminal B (RE+ y Her2+) y tres grupos que no expresan receptor de estrógeno (RE-), e incluyen a los tumores Her2 , tumores "normal like" y tumores "basal like" cuya mayoría son triple negativo (TN). Durante el proceso tumorigénico mamario se acumulan alteraciones tanto genéticas como epigenéticas. A diferencia de las secuencias genéticas, que suelen ser altamente conservadas, las modificaciones epigenéticas revelan un dinamismo diferente. Durante los procesos tumorigénicos estas modificaciones se ven desreguladas, generándose una hipometilación genómica global y una hipermetilación en regiones reguladoras del genoma. Las proteínas ID (inhibitor of DNA binding) son reguladores transcripcionales que controlan la diferenciación de células madres y células progenitoras durante el desarrollo y la vida adulta. A la fecha se han descrito 4 miembros de esta familia: ID1, ID2, ID3 e ID4. En particular, para ID4 se ha postulado que cumple un rol tumor supresor en algunos tipos tumorales como vejiga, colon y leucemias; pero su función en tumores mamarios es controversial donde se ha descrito un rol tanto tumor supresor como oncogénico. Análisis de data mining de la base TCGA (The Cancer Genome Atlas) revelan que la expresión de ID4 es alta en tejido mamario normal y en tumores mamarios del subtipo TN (RE-), mientras que su expresión se ve reducida en tumores luminales A y luminales B (RE+). Es decir que ID4 pareciera tener un rol dual dependiendo del contexto celular. Dado que a la fecha no se han caracterizado mutaciones para ID4 y se postula que la regulación de su expresión es epigenética es que hipotetizamos que: existe una regulación epigenética diferencial de ID4 en tumores mamarios. Para poner a prueba nuestra hipótesis planteamos: a)-Determinar si los niveles de estrógeno median la metilación de ID4 en tumores mamarios; b)-Evaluar si EZH2 participa de la metilación de ID4 en tumores mamarios. Consideramos que nuestro proyecto contribuirá al conocimiento de la regulación epigenética de ID4 en la carcinogénesis mamaria. |
| descriptores_str_mv |
Cancer de mama Metilación Neoplasias de la mama Oncología |
| disciplina_str_mv |
Ciencias e Investigación Ciencias médicas |
| titulo_str_mv |
Estudio de la regulación epigenética de ID4 en cáncer de mama Study of the epigenetic role of ID4 in breast cancer |
| dependencia_str_mv |
Facultad de Ciencias Médicas |
| object_type_str_mv |
Textual: Investigación |
| id |
14714 |
| plantilla_str |
Informe de Investigación |
| record_format |
Informe de Investigación |
| tipo_str |
textuales |
| type_str_mv |
Articulos |
| title_full |
Estudio de la regulación epigenética de ID4 en cáncer de mama |
| title_fullStr |
Estudio de la regulación epigenética de ID4 en cáncer de mama Estudio de la regulación epigenética de ID4 en cáncer de mama |
| title_full_unstemmed |
Estudio de la regulación epigenética de ID4 en cáncer de mama Estudio de la regulación epigenética de ID4 en cáncer de mama |
| description |
Breast cancer is the leading cause of death in women in both developed and developing countries. From the biological point of view, it is an heterogeneous disease that includes a set of biologically different entities. Molecularly, breast tumors are classified into five groups: two groups that express estrogen receptor (ER), which include tumors of type Luminal A (ER + and Her2-) and type Luminal B (ER + and Her2 +) and three groups that do not express estrogen receptor (ER-), and include Her2 tumors, "normal like" and "basal like" tumors whose majority are triple negative (TN). During the mammary tumorigenic process, both genetic and epigenetic alterations accumulate. Unlike genetic sequences, which are usually highly conserved, epigenetic modifications reveal a different dynamism. During the tumorigenic processes these modifications are deregulated, generating global genomic hypomethylation and hypermethylation in regulatory regions of the genome. ID (inhibitor of DNA binding) proteins are transcriptional regulators that control the differentiation of stem cells and progenitor cells during development and adult life. To date, 4 members of this family have been described: ID1, ID2, ID3 and ID4. For ID4 it has been postulated that it has a tumor suppressive role in some tumor types such as bladder, colon and leukemias; but its role in mammary tumors is controversial where both suppressive and oncogenic functions have been described. Data mining analysis of TCGA (The Cancer Genome Atlas) reveal that the expression of ID4 is high in normal mammary tissue and mammary tumors of the TN subtype (RE-), while its expression is reduced in luminal tumors A and luminal B tumors (RE +). That is to say that ID4 seems to have a dual role depending on the cellular context. Given that, to date, no mutations for ID4 have been characterized and that the main mechanism for gene regulation is through promoter methylation, we hypothesize that: there is a differential epigenetic regulation of ID4 in TN and non-TN mammary tumors. To test our hypothesis we propose: a) -Determine if estrogen levels mediate ID4 methylation in mammary tumors; b) -Evaluate whether EZH2 participates in the methylation of ID4 in mammary tumors. We consider that our project will contribute to the knowledge of the epigenetic regulation of ID4 in mammary carcinogenesis. |
| title |
Estudio de la regulación epigenética de ID4 en cáncer de mama |
| spellingShingle |
Estudio de la regulación epigenética de ID4 en cáncer de mama Cancer de mama Metilación Neoplasias de la mama Oncología Branham, María Teresita Lurito, Sergio Roberto Nasif, Daniela Lucía Roqué Moreno, María |
| topic |
Cancer de mama Metilación Neoplasias de la mama Oncología |
| topic_facet |
Cancer de mama Metilación Neoplasias de la mama Oncología |
| publishDate |
2019 |
| author |
Branham, María Teresita Lurito, Sergio Roberto Nasif, Daniela Lucía Roqué Moreno, María |
| author_facet |
Branham, María Teresita Lurito, Sergio Roberto Nasif, Daniela Lucía Roqué Moreno, María |
| tags_str_mv |
siip2019-2021 |
| title_sort |
Estudio de la regulación epigenética de ID4 en cáncer de mama |
| title_short |
Estudio de la regulación epigenética de ID4 en cáncer de mama |
| url |
https://bdigital.uncu.edu.ar/fichas.php?idobjeto=14714 |
| estado_str |
3 |
| building |
Biblioteca Digital |
| filtrotop_str |
Biblioteca Digital |
| collection |
Informe de Investigación |
| institution |
Sistema Integrado de Documentación |
| indexed_str |
2023-04-25 00:35 |
| _version_ |
1764120126080155648 |
