Compositions and methods are provided for the treatment and diagnosis of diseases associated with the expression of one or more of the betaI, betaII, gamma, delta, epsi, ζ or eta isoforms (isozymes) of protein kinase C (PKC). Oligonucleotides are provided which are targeted to nucleic acids encoding PKC-betaI, PKC-betaII, PKC-gamma, PKC-delta, PKC-epsi, PKC-ζ or PKC-eta. Provided herein are oligonucleotides specifically hybridizable with a translation initiation site, 5'-untranslated region, 3'-untranslated region or other targeted region of a betaI, betaII, gamma, delta, epsi, ζ or eta isoform of PKC, wherein at least about 75% of the nucleoside units of a given oligonucleotide are joined together by a stereospecific (i.e., Sp or Rp) phosphorothioate 3' to 5' linkages. In preferred embodiments, the oligonucleotides of the disclosure additionally contain one or more chemical modifications. Also disclosed are methods of using the oligonucleotides of the invention for modulating the expression of at least one of the betaI, betaII, gamma, delta, epsi, ζ or eta isoforms of PKC and for treating animals suffering from disease amenable to therapeutic intervention by modulating the expression of one or more of the betaI, betaII, gamma, delta, epsi, ζ or eta isoforms of PKC.