Article ; Online: Overexpression of WT1 in all molecular subtypes of breast cancer and its impact on survival: exploring oncogenic and tumor suppressor roles of distinct WT1 isoforms.
2024 Volume 51, Issue 1, Page(s) 544
Abstract: Background: Breast cancer is a highly heterogeneous solid tumor, posing challenges in developing targeted therapies effective for all mammary carcinoma subtypes. WT1 emerges as a promising target for breast cancer therapy due to its potential oncogenic ... ...
| Abstract | Background: Breast cancer is a highly heterogeneous solid tumor, posing challenges in developing targeted therapies effective for all mammary carcinoma subtypes. WT1 emerges as a promising target for breast cancer therapy due to its potential oncogenic role in various cancer types. Previous works have yielded inconsistent results. Therefore, further studies are needed to clarify the behavior of this complex gene in breast cancer. Methods and results: In this study, we examined WT1 expression in both Formalin Fixed Paraffin Embedded breast tumors (n = 41) and healthy adjacent tissues (n = 41) samples from newly diagnosed cases of ductal invasive breast cancer. The fold change in gene expression between the tumor and healthy tissue was determined by calculating 2 Conclusions: Interestingly, this overexpression was observed in all molecular subtypes of invasive breast cancer, underscoring the significance of WT1 as a potential target in all these subtypes. The observed WT1 down-expression in a few cases of invasive breast cancer, associated with better survival outcomes, may correspond to the down-regulation of a particular WT1-KTS (-) isoform: the WT1 A isoform (EX5-/KTS-). The co-expression of this WT1 oncogenic isoform with a regulated WT1- tumor suppressor isoform, such as the major WT1 F isoform (EX5-/KTS +), could also explain such survival outcomes. Due to its capacity to adopt dual roles, it becomes imperative to conduct individual molecular expression profiling of the WT1 gene. Such an approach holds great promise in the development of personalized treatment strategies for breast cancer. |
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| MeSH term(s) | Female ; Humans ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Genes, Tumor Suppressor ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; WT1 Proteins/genetics ; WT1 Proteins/metabolism | |||||
| Chemical Substances | Protein Isoforms ; WT1 protein, human ; WT1 Proteins | |||||
| Language | English | |||||
| Publishing date | 2024-04-20 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 186544-4 | |||||
| ISSN | 1573-4978 ; 0301-4851 | |||||
| ISSN (online) | 1573-4978 | |||||
| ISSN | 0301-4851 | |||||
| DOI | 10.1007/s11033-024-09450-4 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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