In vitro and in vivo analysis of B-Myb in basal-like breast cancer
| العنوان: | In vitro and in vivo analysis of B-Myb in basal-like breast cancer |
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| المؤلفون: | Scott Winkel, Robert C. Millikan, Aaron R. Thorner, Charles M. Perou, Joel S. Parker, Katherine A. Hoadley |
| المصدر: | Oncogene |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Cancer Research, MYBL2, Cell Cycle Proteins, basal-like, medicine.disease_cause, 0302 clinical medicine, Risk Factors, Genotype, Tumor Cells, Cultured, Topoisomerase II Inhibitors, MYB, Enzyme Inhibitors, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Cell cycle, Prognosis, 3. Good health, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Breast disease, B-Myb, Antineoplastic Agents, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, breast cancer, Breast cancer, Antigens, Neoplasm, Genetics, medicine, Humans, Genetic Predisposition to Disease, Molecular Biology, Germ-Line Mutation, 030304 developmental biology, Gene Expression Profiling, Cancer, medicine.disease, Survival Analysis, Gene expression profiling, DNA Topoisomerases, Type II, Carcinoma, Basal Cell, Drug Resistance, Neoplasm, Immunology, Trans-Activators, Cancer research, Carcinogenesis |
| الوصف: | A defining feature of basal-like breast cancer, a breast cancer subtype with poor clinical prognosis, is the high expression of “proliferation signature” genes. We identified B-Myb, a MYB family transcription factor that is often amplified and overexpressed in many tumor types, as being highly expressed in the proliferation signature. However, the roles of B-Myb in disease progression, and its mammary-specific transcriptional targets, are poorly understood. Here, we demonstrated that B-Myb expression is a significant predictor of survival and pathological complete response to neoadjuvant chemotherapy in breast cancer patients. We also identified a significant association between the G/G genotype of a nonsynonymous B-Myb germline variant (rs2070235, S427G) and an increased risk of basal-like breast cancer [OR 2.0, 95% CI (1.1-3.8)]. In immortalized, human mammary epithelial cell lines, but not basal-like tumor lines, cells ectopically expressing wild-type B-Myb or the S427G variant showed increased sensitivity to two DNA topoisomerase IIα inhibitors, but not to other chemotherapeutics. In addition, microarray analyses identified many G2/M genes as being induced in B-Myb overexpressing cells. These results confirm that B-Myb is involved in cell cycle control, and that dysregulation of B-Myb may contribute to increased sensitivity to a specific class of chemotherapeutic agents. These data provide insight into the influence of B-Myb in human breast cancer, which is of potential clinical importance for determining disease risk and for guiding treatment. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7203c3980d7b23069b7572028fce93b7Test https://doi.org/10.1038/onc.2008.430Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7203c3980d7b23069b7572028fce93b7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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