• Protein phosphatase4 (PP4) is over-expressed in breast cancer tissue samples and in breast cancer cell lines (hormone receptor positive cell line-MCF7 and triple negative cell line -MDA-MB-231).
• Over-expression of PP4c (protein phospahtase4 catalytic subunit) in both MCF7 and in MDA-MB-231 resulted in reduced cell number, increased apoptosis and reduced cell migration.
• Down-regulation of PP4c in both MCF7 and in MDA-MB-231 increased cell number reduced apoptosis and increased cell migration.
• PP4c effects on cell survival, migration and apoptosis are mediated at least partly by PEA15 (phosphoprotein enriched in astrocytes 15).
• PP4c down regulation reduced sensitivity of MCF7 and MDA-MB-231 to DNA damaging agents such as cisplatin and doxorubicin and also reduced sensitivity of MCF7 and MDA-MB-231 to mTOR1 inhibitor agents such as rapamycin and everolimus.
• PP4c down regulation reduced sensitivity of MCF7 to Akt inhibitor, dual mTOR1,2 inhibitors and to PI3K inhibitor. On the other hand, PP4c down regulation in MDA-MB-231 increased sensitivity of MD-MB-231 cells to Akt inhibitor, dual mTOR1,2 inhibitors and had no effect on the response of MD-MB-231 cells to PI3K inhibitor.
• PP4c down-regulation in MCF7 cells increased the phosphorylation of (4EBP1, GSK3-a, PDK1, Bad, S6ribosomal protein, PTEN, PRAS40).
• PP4c down regulation in MDA-MB-231 increased the phosphorylation of PDK1, Bad, PTEN, and PRAS40, but reduced the phosphorylation of 4EBP1, GSK3-a, S6ribosomal protein.
Discuss the following: The above data showed that PP4c play an important role in regulation of breast cancer cell functions and in controlling response of these cells to various chemotherapeutic agents by targeting important proteins in the Akt- mTOR pathway that are playing an important role in regulation of cell functions. 1-Link the above results to each other and compare them with other researches and articles. 2- Identify which pathways that PP4c targeting to produce its function in MCF7 and in MDA-MB-231, and how the differences in these pathways and the targeted proteins effect on the response of these cells to various chemotherapeutic agents. 3- look at the pathway and see if one of the upstream kinase is dephosphorylated/inactivated by PP4c . If you find one, this means by deactivating the kinase you are affecting the phosphorylation levels of the proteins that are usually phosphorylated by this kinase.