Expression of RUNX3 in skin cancers

Abstract

Background. Expression of Runt-related transcription factor 3 (RUNX3) is reduced in a large number of cancers. However, a few studies have reported higher expression of RUNX3 in several cancers, including basal cell carcinoma (BCC). In light of this, we explored the expression of RUNX3 in skin cancers generally, to determine whether it acts as an oncogene or a tumour-suppressor gene in skin tumours. Aim. To investigate the expression of RUNX3 in normal skin and malignant skin tumours. Methods. RUNX3 expression was evaluated by western blotting in 24 specimens, comprising 6 malignant melanoma (MM), 6 squamous cell carcinoma (SCC), 6 BCC and 6 normal skin specimens. Immunohistochemical staining was carried out to analyse RUNX3 expression in 16 MM, 16 SCC and 16 BCC specimens. To identify where the protein was expressed, the cytoplasmic and nuclear protein expression of RUNX3 in skin cancer tissues was determined. A cell-proliferation study was performed on an MM line (G361) by small interfering (si) RNA transfection. Results. The western blotting experiments showed that RUNX3 was not expressed in normal skin tissues, but it was overexpressed in all MM and SCC samples, and in five of the six BCC samples. Using immunochemistry, RUNX3 was found to be overexpressed in all cancer tissues analysed. Subcellular fraction analysis revealed that RUNX3 was expressed in the nuclei but not the cytoplasm of all the skin cancer tissues analysed, and RUNX3 silencing by siRNA in G361 cells resulted in a decrease in proliferation. Conclusions. Based on these results, we suggest that RUNX3 has an oncogenic potential and does not act as a tumour suppressor in skin cancers.