Elevated expression of ERK 2 in Acc treated with PD98059

Objective:Adenoid cystic carcinoma (ACC) is a familiar malignant tumor of salivary gland. We examined the effect of chronic exposure of tumor cells to a mitogen-activated protein kinase/extracellular signal-regulated kinases (ERK) kinase inhibitor, PD98059, on cell proliferation was investigated. Methods:ACC were cultured in the presence of PD98059 for more than 4 weeks and proliferation and signal transduction pathways were examined. PD98059 significantly inhibited the proliferation of parental cells. Results:PD98059 failed to inhibit proliferation of ACC-M cells significantly. Expression of ERK 1 and 2 was elevated in these cells. These phenotypes were reversible. Downregulation of ERK 2, but not ERK 1, by small interfering RNA significantly inhibited the proliferation of ACC-M cells. Taken together, chronic exposure of tumor cells to PD98059 induced elevated expression of ERK 2, which was associated with decreased sensitivity of cellular proliferation to PD98059. Conclusion:Treatment of patients with a ERK inhibitor in combination with inhibitors of protein synthesis or translation could be an important option for future clinical studies. Keywords: Adenoid cystic carcinoma; ERK; Proliferation