The expression of uPAR is affected by NO, HIF-1α, and ERK in MDA-MB-231 breast carcinoma cell line under hypoxic condition : uPAR expression nder hypoxic conditions depends on iNOS mod lated ERK phosphorylation in MDA-MB-231 breast carcinoma cell line

다국어 초록 (Multilingual Abstract)

Introduction: Hypoxic stress underlies a number of important biological processes in cancer invasion and metastasis. Urokinase plasminogen activator receptor (uPAR) is known to play a major role in cancer invasion and metastasis and the level of uPAR expression correlates with poor prognosis in various cancer types. In hypoxic states, the expression of uPAR is increased. Nitric oxide (NO) and inducible nitric oxide synthase (iNOS) are important products for hypoxic stress. Human breast carcinoma cells and mouse mammary tumor cell lines produce NO which is correlated with tumor grade and metastasis. NO may activate or modulate extracellular signal regulated kinase (ERK).
Purpose: However, the molecular interactions between iNOS, NO, ERK and uPAR have not yet been fully evaluated yet. We have evaluated urokinase plasminogen activator (uPA), uPAR, ERK and hypoxia inducible factor 1α (HIF-1α) expression under hypoxic conditions in the MDA-MB-231 human breast cancer cell line, which is known to have highly invasive and metastatic potential.
Methods and Materials: we used MDA-MB-231 human breast carcinoma cell line. Cells were incubated in a hypoxic or normoxic incubator and treated with PD98059 (ERK inhibitor) and aminoguanidine (iNOS inhibitor). After treatment hypoxia or drug, cells were harvested and then to see uPAR, ERK phosphorylation, and HIF-1α expression, Western blot was performed. To see uPA activity, media were collected and then gel zymography was performed.
Results: HIF-1α, uPAR, p-ERK expression, and uPA activity were increased under hypoxic conditions. When we treated MDA-MB-231 cells with a PD98059, uPAR expression was downregulated. However, aminoguanidine markedly increased ERK phosphorylation in a dose dependent manner. Furthermore, aminoguanidine reversed the inhibition of uPAR expression by PD98059.
Conclusion: These results demonstrated that uPAR is induced by hypoxia and increased expression of uPAR is mediated by ERK activation modulated by NO, iNOS in MDA-MB-231 cell line

목차 (Table of Contents)

• [Abstract] = i
• 목차 = iii
• Introduction = 1
• Material and methods = 3
• Results = 6
• Discussion = 8
• Conclusion = 11
• References = 12
• 도표 및 그림 = 19