ABSENCE OF MUTATIONS IN SITES OF KEY FUNCTIONAL IMPORTANCE OF THE RI-ALPHA AND RII-BETA REGULATORY SUBUNITS OF PROTEIN-KINASE-A IN HUMAN BREAST CANCERS

There is evidence that the regulatory subunits (R) of cyclic AMP-depen dent protein kinase A (PKA) are important in the biology of breast can cer and that mutations of both RI alpha and RII beta, alter cellular b ehaviour. Consequently, a PCR-SSCP assay was established to screen for the presence of mutations in and around two functionally important si tes: the pseudophosphorylation site of RI alpha and the autophosphoryl ation site of RII beta, In a cohort of 45 breast cancers, no mutations were found in either area screened. It is concluded that mutation at either of these particular sites is a rare event and is therefore unli kely to be influential in the natural history of most breast cancers. However, the relationship between PKA and breast cancer suggests that it will be important to look for mutations elsewhere as well as identi fying factors that influence the relative expression of the regulatory subunits.