Increased expression of the RI alpha subunit of the cAMP-dependent proteinkinase A is associated with advanced stage ovarian cancer

The primary element in the cAMP signal transduction pathway is the cAMP-dep endent protein kinase (PKA). Expression of the Rl alpha subunit of type I P KA is elevated in a variety of human tumours and cancer cell lines. The pur pose of this study was to assess the prognostic importance of Rl alpha expr ession in patients with ovarian cancer. We have evaluated the expression of Rl alpha in a panel of human ovarian tumours (n = 40) and five human ovari an cancer cell lines using quantitative reverse transcription polymerase ch ain reaction (RT-PCR) and Western blot analysis. The human ovarian cell lin es OAW42 and OTN14 express high endogenous levels of Rl alpha mRNA and prot ein (at significantly higher mRNA levels than high tissue expressors, P < 0 .05). The ovarian cell line A2780 expresses tow endogenous levels of Rl alp ha mRNA and protein (also at higher mRNA levels than low tissue expressors, P < 0.05). Quantitative RT-PCR revealed no significant difference in Rl al pha mRNA expression between different ovarian histological subtypes in this study. No associations were found between Rl alpha mRNA expression and dif ferentiation state. Rl alpha mRNA expression was significantly associated w ith tumour stage (P = 0.0036}, and this remained significant in univariate analysis (P = 0.0002). A trend emerged between Rl alpha mRNA expression lev els and overall survival in univariate analysis (P = 0.051), however, by mu ltivariate analysis, stage remained the major determinant of overall surviv al (P = 0.0001). This study indicates that in ovarian epithelial tumours hi gh Rl alpha mRNA expression is associated with advanced stage disease. Rl a lpha expression may be of predictive Value in ovarian cancer and may be ass ociated with dysfunctional signalling pathways in this cancer type.