McDaid H M, Cairns M T, Atkinson R J, McAleer S, Harkin D P, Gilmore P, Johnston P G
Department of Oncology, The Queen's University of Belfast, Belfast City Hospital, UK.
Br J Cancer. 1999 Feb;79(5-6):933-9. doi: 10.1038/sj.bjc.6690149.
The primary element in the cAMP signal transduction pathway is the cAMP-dependent protein kinase (PKA). Expression of the RIalpha subunit of type I PKA is elevated in a variety of human tumours and cancer cell lines. The purpose of this study was to assess the prognostic importance of RIalpha expression in patients with ovarian cancer. We have evaluated the expression of RIalpha in a panel of human ovarian tumours (n = 40) and five human ovarian cancer cell lines using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The human ovarian cell lines OAW42 and OTN14 express high endogenous levels of RIalpha mRNA and protein (at significantly higher mRNA levels than high tissue expressors, P < 0.05). The ovarian cell line A2780 expresses low endogenous levels of RIalpha mRNA and protein (also at higher mRNA levels than low tissue expressors, P < 0.05). Quantitative RT-PCR revealed no significant difference in RIalpha mRNA expression between different ovarian histological subtypes in this study. No associations were found between RIalpha mRNA expression and differentiation state. RIalpha mRNA expression was significantly associated with tumour stage (P = 0.0036), and this remained significant in univariate analysis (P = 0.0002). A trend emerged between RIalpha mRNA expression levels and overall survival in univariate analysis (P = 0.051), however, by multivariate analysis, stage remained the major determinant of overall survival (P = 0.0001). This study indicates that in ovarian epithelial tumours high RIalpha mRNA expression is associated with advanced stage disease. RIalpha expression may be of predictive value in ovarian cancer and may be associated with dysfunctional signalling pathways in this cancer type.
环磷酸腺苷（cAMP）信号转导途径中的主要元件是cAMP依赖性蛋白激酶（PKA）。I型PKA的RIα亚基在多种人类肿瘤和癌细胞系中表达升高。本研究的目的是评估RIα表达在卵巢癌患者中的预后重要性。我们使用定量逆转录聚合酶链反应（RT-PCR）和蛋白质印迹分析，评估了一组人类卵巢肿瘤（n = 40）和五种人类卵巢癌细胞系中RIα的表达。人类卵巢癌细胞系OAW42和OTN14表达高水平的内源性RIα mRNA和蛋白质（mRNA水平显著高于高组织表达者，P < 0.05）。卵巢癌细胞系A2780表达低水平的内源性RIα mRNA和蛋白质（mRNA水平也高于低组织表达者，P < 0.05）。定量RT-PCR显示，在本研究中不同卵巢组织学亚型之间RIα mRNA表达无显著差异。未发现RIα mRNA表达与分化状态之间存在关联。RIα mRNA表达与肿瘤分期显著相关（P = 0.0036），在单变量分析中这一相关性仍然显著（P = 0.0002）。在单变量分析中，RIα mRNA表达水平与总生存期之间出现了一种趋势（P = 0.051），然而，通过多变量分析，分期仍然是总生存期的主要决定因素（P = 0.
