LKB1 catalytic activity contributes to estrogen receptor alpha signaling
| Autor: | Paola A. Marignani, Suchita Nath-Sain |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Blotting Western P300-CBP Transcription Factors Biology Protein Serine-Threonine Kinases Transfection Catalysis Cell Line Transactivation Germline mutation Breast cancer AMP-Activated Protein Kinase Kinases Cell Line Tumor Coactivator medicine Humans Immunoprecipitation p300-CBP Transcription Factors RNA Small Interfering skin and connective tissue diseases Luciferases Promoter Regions Genetic Molecular Biology Glutathione Transferase Cell Nucleus Estradiol Kinase Reverse Transcriptase Polymerase Chain Reaction Estrogen Receptor alpha Cell Biology Articles medicine.disease Gene Expression Regulation Neoplastic Microscopy Fluorescence Mutation Cancer research Signal transduction Estrogen receptor alpha Signal Transduction |
| Zdroj: | Molecular biology of the cell. 20(11) |
| ISSN: | 1939-4586 |
| Popis: | The tumor suppressor serine-threonine kinase LKB1 is mutated in Peutz-Jeghers syndrome (PJS) and in epithelial cancers, including hormone-sensitive organs such as breast, ovaries, testes, and prostate. Clinical studies in breast cancer patients show low LKB1 expression is related to poor prognosis, whereas in PJS, the risk of breast cancer is similar to the risk from germline mutations in breast cancer (BRCA) 1/BRCA2. In this study, we investigate the role of LKB1 in estrogen receptor alpha (ERalpha) signaling. We demonstrate for the first time that LKB1 binds to ERalpha in the cell nucleus in which it is recruited to the promoter of ERalpha-responsive genes. Furthermore, LKB1 catalytic activity enhances ERalpha transactivation compared with LKB1 catalytically deficient mutants. The significance of our discovery is that we demonstrate for the first time a novel functional link between LKB1 and ERalpha. Our discovery places LKB1 in a coactivator role for ERalpha signaling, broadening the scientific scope of this tumor suppressor kinase and laying the groundwork for the use of LKB1 as a target for the development of new therapies against breast cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|