Protein kinase C (PKC) comprises a family of highly related serine/threonine protein kinases involved in multiple signaling pathways, which control cell proliferation, survival, and differentiation. The role of PKCα in cancer has been studied for many years. However, it has been impossible to establish whether PKCα acts as an oncogene or a tumor suppressor.

Here, we analyzed the importance of PKCα in cellular processes such as proliferation, migration, or apoptosis by inhibiting its gene expression in a luminal A breast cancer cell line (MCF-7) using a specific siRNA agains PKCα . In addition, differential expression analysis (microarray) and phospho-kinase arrays of PKCα-KD vs PKCα-WT MCF-7 were performed to analyze the molecular pathways altered in MCF-7 breas cancer cells by decreasing PKCα protein expression.

The results indicated that PKCα depletion reduces the tumor phenotype mainly by decreasing the proliferation and migration of this breast cancer model. Differential expression analysis and phospho-kinase arrays of PKCα-KD vs PKCα-WT MCF-7 identified an essential set of proteins and oncogenic kinases of the JAK/STAT and PI3K/AKT pathways that were down-regulated, whereas IGF1R, ERK1/2, and p53 were up-regulated. In addition, unexpected genes related to the interferon pathway appeared down-regulated, while PLC, ERBB4, or PDGFA dis-played up-regulated.

The results of this study suggest that PKCα plays an oncogenic role in this type of breast cancer model. The integration of this information clearly showed us the usefulness of inhibiting a multifunctional kinase-like PKCα in the first step to control the tumor phenotype. Then allowing us to design a possible selection of specific inhibitors for the unexpected up-regulated pathways to further provide a second step of treatment to inhibit the proliferation and migration of MCF-7 cells.