Hiba Mohammed (Three Minute Thesis)
Institute for Science and Technology in Medicine
Protein phosphatase 4 regulates cell survival and responses to
PI3K/AKT/mTOR pathway inhibitors in breast cancer cell lines
Background:
Protein phosphatase 4 (PP4) is a PP2A-related serine/threonine phosphatase which
has already been implicated in the control of cell proliferation, cell cycle and
tumorigenesis. We have previously identified the catalytic subunit of PP4 (PP4c) as
an important gene in the regulation of both apoptosis and cell proliferation in breast
cancer cells. The aims of this study were to examine the effects of reducing the
expression of PP4c on breast cancer cell survival and their responses mTOR, Akt
and PI3K inhibitors.
Material and method:
MCF7 and MDA-MB-231 were transfected with siRNAs to different PP4c sequences,
controls received scrambled siRNA. Culture viability, migration, long term survival
and apoptosis were assessed post transfection. In some experiments, transfected
cells were exposed to chemotherapeutic drugs post-transfection to induce apoptosis,
then culture viability and apoptosis were assessed.
Results:
siRNA mediated silencing of PP4 enhanced the proliferation and survival of MCF7
and MDA-MB-231 cells and increased their colony forming and cell migration
abilities. In MCF7 cells, reduced PP4c expression decreased their sensitivity to
mTOR, Akt and PI3K inhibitors. However, a reduction in PP4c levels in MDA-MB-231
sensitised the cells to mTOR, Akt and PI3K/mTOR inhibitors but had no effects on
the response to PI3K inhibitor.
Conclusion:
Our results reveal a complex role of PP4 in controlling breast cancer cell survival and
highlight the importance of identifying the signalling pathways regulated by PP4c and
its role in the development and treatment of breast cancer.
Acknowledgement:
This study funded by the Ministry of Higher Education and Scientific Research,
Republic of Iraq.
Postgraduate Conference 2016
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