The Glucocorticoid receptor (GR) and the tissue specific transcription factor PAX6 act synergistically to enhance expression of genes associated with migration and metastasis
By
Ingvild Mikkola
Associate professor (PhD)
Research group of Pharmacology
Department of Pharmacy
Faculty of Health Sciences
University of Tromsø – The Arctic University of Norway
Glucocorticoids (GCs) regulate important biological functions like inflammation and immune responses, glucose and lipid metabolism, bone density, circadian rhythm and stress responses. The effects of GCs are mediated by the glucocorticoid receptor (GR) which is a transcription factor (TF) belonging to the nuclear receptor superfamily. It is ubiquitously expressed, and yet an enormous variation in target genes and biological processes regulated by GR is observed in a context dependent manner. Since GCs have anti-inflammatory effects and work as immune suppressors they are widely used in the clinic. Further, they cause apoptosis in lymphoid cancer cells, and are therefore used as first lane treatment for this disease. For treatment of non-hematological cancers, GCs are often used to relieve side effects from chemotherapy or irradiation.
PAX6 is a tissue specific TF important for proper embryo development, and its expression is downregulated but maintained in adult tissues. It is expressed in specific regions of the brain and spinal cord, the eye, nose and pancreas. It is also expressed in several cancers (e.g glioblastoma, pancreatic adenocarcinoma, retinoblastoma, non-small cell lung cancer), but its role in cancer is not clarified.
We observe that PAX6 and GR synergistically enhance transcription of the Matrix metalloproteinase 2 (MMP2) gene and other genes associated with migration and metastasis. We are the first to report an interaction between GR and PAX6, and the molecular investigation of this interaction will be presented in this seminar.
Since several tumors are known to be PAX6 positive and GCs are used to treat cancer patients, an important future goal will be to clarify whether GC treatment of patients with PAX6 positive tumors causes an increase in genes regulating migration and metastasis, and thus a higher risk of metastatic tumors.
Welcome to the seminar
Arr.: RNA and Molecular Pathology