Investigating RUNX1 and RUNX2 in prostate cancer
| Autor: | Karen Blyth, Ewan R. Cameron, Anne Jane McKillop, Joanne Edwards, Emma Johnson, Susan M. Mason |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology PCA3 Cancer Research medicine.medical_specialty Chemotherapy business.industry medicine.medical_treatment Incidence (epidemiology) Cancer Disease medicine.disease 03 medical and health sciences Prostate cancer 030104 developmental biology Internal medicine embryonic structures Medicine business Hormone |
| Zdroj: | Journal of Clinical Oncology. 35:232-232 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2017.35.6_suppl.232 |
| Popis: | 232 Background: Prostate cancer is the most commonly diagnosed cancer in men and is increasing in incidence. Current treatment for metastatic disease is initially hormone treatment and chemotherapy. While this produces a response in the vast majority of patients, it is not curative. Novel therapeutic agents could provide a further treatment strategy and it is therefore important to understand the molecular pathways which contribute to this disease. The RUNX family of genes have been implicated as both oncogenes and tumor suppressors, with their role being context dependent. It has been reported that RUNX2 may have a tumor suppressor role in early stage prostate cancer but that this may switch to an oncogenic role in later stage disease. Methods: This project examines the expression of both RUNX1 and RUNX2 in a tissue microarray (TMA) of human prostate cancers. In parallel to the human studies both RUNX1 and RUNX2 were investigated in murine models of prostate cancer. Results: Analysis of the TMA showed that increasing levels of RUNX2 were associated with increasing Gleason grade, shorter time to relapse and poorer survival; the opposite effect was seen in RUNX1, where low levels of protein expression correlated with shorter survival. In concordance with the human results, reducing levels of RUNX2 in mouse models was associated with delayed tumor initiation, and smaller, less cystic tumors at endpoint. The opposite effect was seen with Runx1 where low levels resulted in more aggressive and invasive disease. Finally, when loss of both genes was combined in a model with loss of Pten and stimulation of WNT, survival was significantly reduced compared to controls. Conclusions: This study suggests that RUNX2 expression may correlate with a poorer prognosis in prostate cancer, while expression of RUNX1 is likely to be associated with an improved outcome. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|