上皮性卵巢癌中自噬基因Beclin 1的表达及其调控相关信号传导途径的研究

目的 研究自噬基因Beclin 1及其调控相关信号传导途径磷酸肌醇-3激酶/蛋白激酶B(PI3K/PKB)与上皮性卵巢癌发生发展之间的关系.方法 用免疫组化的方法对25例正常卵巢组织、25例良性上皮性卵巢肿瘤、19例交界性上皮性卵巢肿瘤及69例上皮性卵巢癌组织进行Beclin 1、Class Ⅰ PI3K (p110α)、Class Ⅲ PI3K(hvps34)及其下游的磷酸化PKB(p-PKB)的表达水平进行检测.结果 Beclin 1、hvps34在正常卵巢组织与良性卵巢肿瘤组织中表达较高,在交界性卵巢肿瘤组织中开始下降,在上皮性卵巢癌中的表达最低(P＜0.05);p110α、p-PKB在交界性卵巢肿瘤组织中开始升高,在上皮性卵巢癌中的表达高于其它3组(P＜0.05).卵巢癌Ⅰ～Ⅱ期、高中分化、淋巴结无转移的卵巢肿瘤组织中Beclin 1的表达分别高于Ⅲ～Ⅳ期、低分化、淋巴结有转移者(P＜0.05),而p110α及p-PKB的表达则分别降低(P＜0.05).结论 自噬基因Beclin 1在上皮性卵巢癌中的表达下调,对自噬起调控作用的PI3K/PKB信号通路中的成分p110α、hvps34、p-PKB存在表达异常,可能与上皮性卵巢癌的发生、发展及临床预后有关.

Expression and Involved Signal Transduction Pathway of Autophagy Gene Beclin 1 in Epithelial Ovarian Cancer

OBJECTIVE: To investigate the relationship between the autophagy gene Beclin 1 involving the PI3K/PKB signaling pathway and the occurrence, development of epithelial ovarian carcinoma. METHODS: The expression of Beclin 1, Class I PI3K (p110alpha), Class III PI3K (hvps34) or p-PKB was, by immunohistochemistry, detected respectively in 25 normal ovarian tissues, 25 benign neoplasia tissues, 19 borderline tissues, and 69 epithelial ovarian carcinoma tissues. RESULTS: The higher expressions of Beclin 1 and hvps34 were found in normal and benign ovarian neoplasia tissues; the expressions were reduced in the borderline lesion tissue; and the lowest level of expressions could be detected in the ovarian carcinoma tissue (P < 0.05). The expressions of p110alpha and p-PKB increased slightly in borderline ovarian tissue, and were higher in the epithelial ovarian carcinoma tissue than other three groups (P < 0.05). Beclin 1 expressions in the epithelial ovarian cancer tissues with stage I - II, high-middle grade differentiation and negative lymph node metastasis were higher than those with stage III - IV, low grade differentiation and positive lymph node metastasis, but the expressions of p110alpha and p-PKB in were lower (P < 0.05). CONCLUSION: Beclin 1 expression is down-regulated in epithelial ovarian cancer tissue while the p110alpha, hvps34 and p-PKB are having the abnormal expressions on PI3K/PKB signaling pathway, which may be correlated with the occurrence and development of epithelial ovarian carcinoma.