Oncogene, 2007-07, Vol.26 (32), p.4668-4678
2007
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- Autor(en) / Beteiligte
- Titel
- Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells
- Ist Teil von
- Oncogene, 2007-07, Vol.26 (32), p.4668-4678
- Ort / Verlag
- Basingstoke: Nature Publishing
- Erscheinungsjahr
- 2007
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Prolactin (PRL) stimulates the cytoskeletal re-organization and motility of breast cancer cells. During PRL receptor signaling, Vav2 becomes phosphorylated and activated, an event regulated by the serine/threonine kinase Nek3. Given the regulatory role of Vav2, the function of Nek3 in PRL-mediated motility and invasion was examined. Overexpression of Nek3 in Chinese hamster ovary transfectants potentiated cytoskeletal re-organization in response to PRL. In contrast, downregulation of Nek3 expression by small-interfering RNA (siRNA) attenuated PRL-mediated cytoskeletal reorganization, activation of GTPase Rac1, cell migration and invasion of T47D cells. In addition, PRL stimulation induced an interaction between Nek3 and paxillin and significantly increased paxillin serine phosphorylation, whereas Nek3 siRNA-transfected cells showed a marked reduction in paxillin phosphorylation. Analysis of breast tissue microarrays also demonstrated a significant up-regulation of Nek3 expression in malignant versus normal specimens. These data suggest that Nek3 contributes to PRL-mediated breast cancer motility through mechanisms involving Rac1 activation and paxillin phosphorylation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/sj.onc.1210264Titel-ID: cdi_proquest_miscellaneous_70703492
- Format
- –
- Schlagworte
- Animals, Biological and medical sciences, Breast cancer, Breast Neoplasms - enzymology, Breast Neoplasms - pathology, Care and treatment, Cell activation, Cell adhesion & migration, Cell Line, Tumor, Cell migration, Cell Movement, Cell physiology, Cell structures and functions, Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes, Cells, Cellular signal transduction, CHO Cells, Cricetinae, Cricetulus, Cytoskeleton, Cytoskeleton - drug effects, Cytoskeleton - ultrastructure, Cytoskeleton, cytoplasm. Intracellular movements, Female, Fundamental and applied biological sciences. Psychology, Gene expression, Genetic aspects, Genetics, Gynecology. Andrology. Obstetrics, Health aspects, Humans, Kinases, Mammary gland diseases, Medical sciences, Molecular and cellular biology, Motility, Neoplasm Invasiveness, NIMA-Related Kinases, Oncology, Paxillin, Paxillin - metabolism, Phosphorylation, Physiological aspects, Prolactin, Prolactin - pharmacology, Protein-Serine-Threonine Kinases - antagonists & inhibitors, Protein-Serine-Threonine Kinases - genetics, Protein-Serine-Threonine Kinases - physiology, Protein-serine/threonine kinase, Proteins, Proto-Oncogene Proteins c-vav - metabolism, rac1 GTP-Binding Protein - metabolism, Rac1 protein, RNA, Small Interfering - pharmacology, Serine - metabolism, Signal transduction, siRNA, Transfection, Tumors