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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| Autores principales: | , , , |
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| Publicado: |
2019
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| Materias: | |
| Acceso en línea: | https://bdigital.uncu.edu.ar/fichas.php?idobjeto=14714 |
| Sumario: | 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. |
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