The Expression and Possible Roles ofp-STAT3 (ser 727) in Cervical Intraepithelial Neoplasia

• Main Authors: Sheau-Fang Yang, 楊曉芳
• Other Authors: Chee-Yin Chai
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/30305339596804477246

碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 92 === Purpose: Signal transducer and activator of transcription 3 (STAT3) has recently been classified as an oncogene, and STAT3 protein constitutive activation was detected in many cancers. However, in contrast to the more well-characterized events of STAT3 activation by tyrosine phosphorylation, regulation of STATs by serine phosphorylation is understood less. The purpose of this study was to evaluate the expression patterns of phospho-serine residue 727 (p-STAT3 (ser 727)) as well as STAT3 in cervical intraepithelial neoplasia (CIN), and to identify the possible role of p-STAT3 (ser 727) in CIN and cervical tumorgenesis. Experimental design: Paraffin-embedded sections from 83 patients including 20 CIN 1, 10 CIN 2, 26 CIN 3, 10 normal cervical epithelium and 17 squamous cell carcinoma (SCC) were collected for this study. Immunohistochemical analysis was performed and the expression and location of p-STAT3 (ser 727) and STAT3 were evaluated. The results were categorized by semiquantitative method and correlated with Ki-67 expression. Results: The proportion of p-STAT3 (ser 727) high-level expressions in nuclei and cytoplasm and of STAT3 high-level expression in cytoplasm were significantly higher in CIN 3 (76.92%, 69.23%, 57.69%) than in CIN 1/2 (13.33%, 13.33%, 16.67%) (p < 0.001, p < 0.001, p = 0.003). In addition, there was no or little expression of p-STAT3 (ser 727) and STAT3 in normal cervical epithelium, while increased immunostaining of p-STAT3 (ser 727) and STAT3 was present in SCC. The nuclear and 5 cytoplasmic presentations of p-STAT3 (ser 727) and STAT3 were correlated with K-67 nuclear presentation (p < 0.001, p < 0.001, p = 0.025, p = 0.030). Conclusion: This is the first study to establish the expression profiles of p-STAT3 (ser 727) and STAT3 in CIN. We propose that STAT3 signaling pathway and its aberrant serine phosphorylation are correlated with cell proliferation and may play a crucial role in progression of CIN and carcinogenesis of cervical cancer. We believe the accomplishment of this project will provide a better understanding of the carcinogenesis of cervical cancer and provide useful information for the discovery of potential anti-cervical cancer drugs.