| The MAPK signal transduction pathway is an important signal transduction system, which mediates cellular responses to growth, differentiation, apoptosis and other physiological courses. It has also been implicated in the pathogenesis of a variety of malignancies. It was found that there were extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), p38/Reactivating kinase (p38/RK) and big MAP kinase (BMK1)/ERK5 MAPK pathways.ERK and p38 MAP kinase are the important members in MAPK cell signal pathway. It was proved that p38 activated highly in squamous cell carcinoma and breast carcinoma, and ERK activated highly in pancreatic carcinoma. When HSV, HIV or EBV infected, p38 activated highly.Condyloma acuminata (CA) is one of sexually transmitted diseases (STD), which is caused by human papillomaviruses (HPVs). Some studies indicated that when HPV16 infected, MAP kinase activity increased; The HPV11E1E4 protein is phosphorylated by PKA and MAPK in genital epithelium. The HPV 16 E5 gene product has been shown to upregulate the activation of MAP kinases ERK1/2 and cellular proliferation promoted by EGF in a ligand-dependent progress. The HPV 16 E5 protein modulates ERK1/2 and p38 MAP kinase activation by an EGFR-independent progress in stressed human keratinocytes.To investigate the mechanism of CA cell signal pathway and find some probably effective ways to inhibit the pathway of CA cell signal transduction, such as finding specific protein kinase inhibitor, may provide new approaches to prevent or treat CA.In order to investigate the expression of activated ERK and p38 in CA, we detected the expression of phosphorylated ERK and p38 in epithelial cells of 50 HPV 6/11 positive CA cases and 25 cases of normal skins (foreskins) with immunohistochemistry technique (En Vision). With the analysis of expression of p-ERK and p-p38, we expect to address the significance of p-ERK and p-p38 in CA cell signal transduction pathway.Materials and Methods50 cases of HPV 6/11 associated CA were diagnosed by in situ hybridization; Expression and distribution of p-ERK and p-p38 in CA lesions and 25 normal human skins (foreskins) were detected by immunohistochemistry technique (En Vision). The primary antibodies werephospho-ERK monoclonal antibody and phospho-p38 MAPK monoclonal antibody. Nucleus stain for p-ERK and p-p38 were regarded as positive. According to the percentage of the positive cells, the semiquantitative analysis was made. Statistical analysis was performed with the Ridit test. In CA cases, we compared the expression of p-ERK with the expression of p-p38 in order to find if there was correlation between them.Results1. In situ hybridization, a large number of HPV 6/11 positive cells were seen in CA lesions, and the positive cells distributed in superspinous and granular layers. There were no HPV 6/11 positive cells in normal epithelium.2. In 50 cases of CA lesions, the expression of p-ERK was significantly higher than that in normal skin (u=4.113, p<0.01). The positive cells mainly distributed in spinous layers, especially in koilacytes. The positive signal located in nucleus and showed brown.In 50 cases of CA lesions, the expression of p-p38 was significantly higher than that in normal skin (u= 4.497, P<0.01). The positive cells mainly distributed in spinous layers, especially in koilocytes. The positive signal located in nucleus and showed brown.3. In 50 cases of CA, we compared the expression level of p-ERK with that of p-p38, we found that there was correlation between the expression of p-ERK and p-p38 (r=0.42, P<0.01).Discussions and Conclusions1. In HPV 6/11 infected CA, the expression of p-ERK and p-p38 were significantly higher than those in normal skin. The data suggest that ERK and p38 protein kinase are more activated in HPV infected epithelium. It suggests that both of ERK and p38 MAPK pathways play the role in MAP kinase signal pathway of keratinocytes in CA. We hypothesis that some genes o... |
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