Paget, Judith A2013-11-072013-11-0720112011Source: Masters Abstracts International, Volume: 49-06, page: 3851.http://hdl.handle.net/10393/28806http://dx.doi.org/10.20381/ruor-19452The role of the atypical PKC iota (PKC&igr;) in breast cancer is unknown. In this study, the expression of PKC&igr; in breast cancer tissue was investigated using tissue microarrays. PKC&igr; was over-expressed in 70% of breast cancers. The expression and activation of PKC&igr; was also elevated in a subset of breast cancer cell lines. Two cell lines with the highest activation and expression of PKC&igr;, T47D and MCF7, have PIK3CA mutations E545K and HI047R respectively. To investigate the effects of PIK3CA mutations on PKC&igr;, stable MCF10A cells expressing E545K and H1047R mutations were generated using retroviral transduction. Western blot analysis showed that these mutations are sufficient to increase PKC&igr; expression and activation. To analyze the role of PKC&igr; in breast cancer pathogenesis, siRNA targeting PKC&igr; were used. MDAMB-231, T47D and MCF7 breast cancer cells treated with siRNA had decreased proliferation compared to control cells. MCF7 and T47D cells treated with siRNA to PKC&igr; had morphological changes associated with senescence, increased SA-beta-Gal activity and decreased BrdU incorporation. These results demonstrate that PKC&igr; is overexpressed in a subset of breast cancers and can promote the growth of breast cancer cells by repressing premature senescence.99 p.enChemistry, Biochemistry.Thesis