Epiregulin Reduces EGFR Expression And Proliferation In OSCC Cell Line

A novel member of the epidermal growth factor (EGF) family, epiregulin (EPR), has shown potential in promoting wound healing and enhancing proliferation in the epithelial tissues and is also involved in a spectrum of epithelial-related malignancies such as colorectal, lung, and bladder carcinoma. More recently, high numbers of EPR transcripts were found on archival oral squamous cell carcinoma (OSCC) specimens, implicating that EPR may play a role in OSCC progression. Objective: To elucidate the effects of EPR on the morphology and proliferation of the H-series OSCC cell lines. Methods: The clinicopathological origin and the expression of epidermal growth factor receptor (EGFR) and ErbB4 of the H-series OSCC cell lines were characterised and selected for downstream experiments. The cell lines were treated with 1 ηg/ml, 10 ηg/ml, and 20 ηg/ml of EPR for 24 and 48 hours in all subsequent experiments. Untreated cells acted as the control which was used for comparison with each treated group. The outcome measures were (i) cell morphological changes, (ii) cell proliferation (cell counts and 5-bromo-2’-deoxy-uridine (BrdU) assays) and (iii) receptor expression. Results: Phase contrast microscopic examination revealed no appreciable morphological changes in the cells regardless of the dose of EPR tested and the different timelines. Cell counts and BrdU assays revealed no significant changes in cell proliferation after EPR treatment. The effect of EPR on the expression of EGFR and ErbB4 receptors were investigated by flow cytometry. Statistical analyses showed that 20 ηg/ml of EPR significantly reduced the density of EGFR expression in the H103 cell line after 24-hour treatment (p=0.049). Conclusions: EPR has no effect on the morphology and proliferation of the H-series OSCC cell lines. However, the significant reduction in EGFR expression after EPR treatment suggests that the growth factor might play an important role in the regulation of EGFR expression.