Differential expression of cAMP-kinase subunits is correlated with growth in rat mammary carcinomas and uterus

Abstract

The expression of the regulatory (RI and RII) and catalytic (C) subunits of cAMP-dependent protein kinase was found to depend on the growth-state in oestrogen-dependent DMBA-induced mammary adenocarcinomas as well as in uteri of the rat. Castration-induced atrophy of the oestrogen-dependent tissues was accompanied by a decrease of the concentration of regulatory subunits (RI and RII) relative to both the catalytic subunit (C) and total protein, decreasing the R/protein and R/C ratios. A hyperplastic burst caused by high-dose oestrogen-replacement treatment was associated with an increased level of RI and little change in RII and C levels. Only minor differences were noted for the expression of mRNA for the alpha and beta subtypes of RI, RII and C between rat uteri from castrated and oestrogen-treated animals, or between mammary tumours from normal and castrated animals. Expression of RI beta-mRNA was detected only in the uterus. Our findings provide an experimental correlate for the reported value of the parameter R/protein in human mammary cancer biopsies to predict prognosis and outcome of therapy. Due to the sensitivity of the R/protein ratio towards changes in extracellular protein content, we recommend the biologically more meaningful R/C ratio in further clinical evaluations of mammary tumour biopsies.