ヒト口腔扁平上皮癌におけるリン酸化型ERKおよびMKP-1の発現について

Abstract

Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli. Extracellular signal-regulated kinase (ERK), a MAPK subfamily, are activated by many oncogenes including ras and raf, which are closely associated with cell growth and differentiation. There is a report that ERK is highly expressed in oral squamous cell carcinoma (OSCC) but it does not include activated forms of ERK (phosphorylated ERK, pERK). Here we examined expression of pERK by immunohistochemical method in 50 OSCC and 7 normal gingival mucosa cases. The positive ratios of immunoreactivity for pERK in nuclei of cells were higher in OSCC than in normal gingival mucosa. Index of pERK was correlated with Ki-67 index. Interestingly, pERK was also expressed in Ki-67 negative cells in OSCC. Next, we investigated distribution and expression of mitogen-activated protein kinase phosphatase-1 (MKP-1), which dephosphorylates and inactivates ERK, by the methods of immunohistochemistry and in situ hybridization (ISH). The distribution of positive signals for protein and mRNA expression of MKP-1 showed almost the same results as demonstrated in pERK. The expression of MKP-1 protein by Western blot analysis was seen in all cases, and the expression in several cases of OSCC was higher than that in normal ginglval mucosa. The results raise a possibility that MKP-1 might be activated in response to ERK activation in cancer cells and suggest that the interaction of two molecules play an important role in proliferation and differentiation of OSCC. Moreover, the assay of MKP-1 expression as well as ERK should provide a good clue to assess the progression or prognosis of OSCC.