Inhibition of Prolactin (PRL)-Induced Proliferative Signals in Breast Cancer Cells by a Molecular Mimic of Phosphorylated PRL, S179D-PRL
| Autor: | Matthew D. Schroeder, Jennifer L. Brockman, Ameae M. Walker, Linda A. Schuler |
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| Rok vydání: | 2003 |
| Předmět: |
endocrine system
medicine.medical_specialty endocrine system diseases Receptors Prolactin Breast Neoplasms Cell Count CHO Cells Biology Endocrinology Cyclin D1 Cell Line Tumor Cricetinae Internal medicine STAT5 Transcription Factor medicine Animals Humans Phosphorylation Receptor Mammary tumor Cell growth Molecular Mimicry Milk Proteins Prolactin DNA-Binding Proteins Cell culture Trans-Activators Cancer research STAT protein Mitogen-Activated Protein Kinases Cell Division hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Endocrinology. 144:5300-5307 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | Posttranslational modifications of prolactin (PRL), including phosphorylation, vary with physiologic state and alter biologic activity. In light of the growing evidence for a role for PRL in proliferation in mammary cancer, we examined the ability of a mimic of phosphorylated human PRL, S179D-PRL, to initiate signals to several pathways in mammary tumor cells alone and in combination with unmodified PRL. Unmodified PRL employed multiple pathways to increase cellular proliferation and cyclin D1 levels in PRL-deficient MCF-7 cells. S179D-PRL was a weak agonist compared with unmodified PRL with regard to cellular proliferation, cyclin D1 levels, and phosphorylation of signal transducer and activator of transcription 5 and ERKs. However, S179D-PRL was a potent antagonist of unmodified PRL to these endpoints. In contrast to the reduced levels of the long isoform of the PRL receptor observed in response to a 3-d incubation with unmodified PRL, S179D-PRL up-regulated expression of this isoform, 4-fold. These studies support the utility of this mutant as a PRL antagonist to proliferative signals in mammary epithelial cells, including a potential role in breast cancer therapeutics. |
| Databáze: | OpenAIRE |
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