A Role for Glial Cell–Derived Neurotrophic Factor–Induced Expression by Inflammatory Cytokines and RET/GFRα1 Receptor Up-regulation in Breast Cancer
| العنوان: | A Role for Glial Cell–Derived Neurotrophic Factor–Induced Expression by Inflammatory Cytokines and RET/GFRα1 Receptor Up-regulation in Breast Cancer |
|---|---|
| المؤلفون: | Jorge S. Reis-Filho, Todd Sk, Richard Poulsom, Ivan Plaza-Menacho, Hunt T, Clare M. Isacke, Selma Esseghir |
| المصدر: | Cancer Research. 67:11732-11741 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Cancer Research, medicine.medical_specialty, Glial Cell Line-Derived Neurotrophic Factor Receptors, Mammaplasty, Breast Neoplasms, Transfection, Paracrine signalling, Neurotrophic factors, Internal medicine, Glial cell line-derived neurotrophic factor, medicine, Humans, Breast, Glial Cell Line-Derived Neurotrophic Factor, RNA, Small Interfering, Autocrine signalling, Oligonucleotide Array Sequence Analysis, Inflammation, biology, Nucleic Acid Hybridization, Up-Regulation, Gene Expression Regulation, Neoplastic, Endocrinology, Oncology, Proto-Oncogene Proteins c-ret, Tumor progression, biology.protein, Cancer research, Cytokines, Female, Tumor promotion, GDNF family of ligands, Cell Division |
| الوصف: | By screening a tissue microarray of invasive breast tumors, we have shown that the receptor tyrosine kinase RET (REarranged during Transfection) and its coreceptor GFRα1 (GDNF receptor family α-1) are overexpressed in a subset of estrogen receptor–positive tumors. Germ line–activating oncogenic mutations in RET allow this receptor to signal independently of GFRα1 and its ligand glial cell–derived neurotrophic factor (GDNF) to promote a spectrum of endocrine neoplasias. However, it is not known whether tumor progression can also be driven by receptor overexpression and whether expression of GDNF, as has been suggested for other neurotrophic factors, is regulated in response to the inflammatory microenvironment surrounding many epithelial cancers. Here, we show that GDNF stimulation of RET+/GFRα1+ MCF7 breast cancer cells in vitro enhanced cell proliferation and survival, and promoted cell scattering. Moreover, in tumor xenografts, GDNF expression was found to be up-regulated on the infiltrating endogenous fibroblasts and to a lesser extent by the tumor cells themselves. Finally, the inflammatory cytokines tumor necrosis factor-α and interleukin-1β, which are involved in tumor promotion and development, were found to act synergistically to up-regulate GDNF expression in both fibroblasts and tumor cells. These data indicate that GDNF can act as an important component of the inflammatory response in breast cancers and that its effects are mediated by both paracrine and autocrine stimulation of tumor cells via signaling through the RET and GFRα1 receptors. [Cancer Res 2007;67(24):11732–41] |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1188790277be2dda69cb5be1dcb54d75Test https://doi.org/10.1158/0008-5472.can-07-2343Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1188790277be2dda69cb5be1dcb54d75 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
|---|