Impaired Turnover of Prolactin Receptor Contributes to Transformation of Human Breast Cells
Autor: | Bentley Varghese, Thai H. Tran, Serge Y. Fuchs, Alexandr Plotnikov, Chengbao Liu, Hallgeir Rui |
---|---|
Rok vydání: | 2009 |
Předmět: |
Cancer Research
medicine.medical_specialty Receptors Prolactin Cell Down-Regulation Breast Neoplasms Cell Growth Processes Biology Article Downregulation and upregulation Cell Line Tumor Internal medicine medicine Humans Neoplasm Invasiveness Breast Phosphorylation Receptor Prolactin receptor Epithelial Cells Prolactin Ubiquitin ligase Cell Transformation Neoplastic medicine.anatomical_structure Endocrinology Oncology Cancer cell biology.protein Cancer research Signal transduction Signal Transduction |
Zdroj: | Cancer Research. 69:3165-3172 |
ISSN: | 1538-7445 0008-5472 |
Popis: | Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). PRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the βTrcp E3 ubiquitin ligase and facilitates PRLr degradation. Here, we show that an impaired PRLr turnover results in an augmented PRL signaling and PRL-induced transcription. Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth. Conversely, a decrease in PRLr levels achieved by either pharmacologic or genetic means in human breast cancer cells dramatically reduced transformation and tumorigenic properties of these cells. Consequences of alteration of PRLr turnover for homeostasis of mammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed. [Cancer Res 2009;69(7):3165–72] |
Databáze: | OpenAIRE |
Externí odkaz: |