Absence of mutations in sites of key functional importance of the RIα and RIIβ regulatory subunits of protein kinase A in human breast cancers

There is evidence that the regulatory subunits (R) of cyclic AMP-dependent protein kinase A (PKA) are important in the biology of breast cancer and that mutations of both RIα and RIIβ, alter cellular behaviour. Consequently, a PCR-SSCP assay was established to screen for the presence of mutations in and around two functionally important sites: the pseudophosphorylation site of RIα and the autophosphorylation site of RIIβ. 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 unlikely 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 identifying factors that influence the relative expression of the regulatory subunits.