OAR@UM Collection:https://www.um.edu.mt/library/oar/handle/123456789/635082026-04-18T19:35:09Z2026-04-18T19:35:09ZThe PP2A activator FTY720 reduced viability in a subset of breast cancer cell lineshttps://www.um.edu.mt/library/oar/handle/123456789/400582020-11-09T09:06:36Z2016-01-01T00:00:00ZTitle: The PP2A activator FTY720 reduced viability in a subset of breast cancer cell lines
Abstract: Introduction and Aims: Protein phosphatase 2A (PP2A) is a serine-threonine tumour suppressor
phosphatase that is frequently deregulated in cancer, including breast cancer. Interestingly,
pharmacological restoration of PP2A correlates with anti-neoplastic properties. The aims of the study
are to evaluate the sensitivity of a panel of breast cancer cell lines to the PP2A activator FTY720, and
to identify a set of genes that correlate with cellular viability in the sensitive breast cancer cell lines
following FTY720 exposure.
Methodology: A total of 11 breast cancer cell lines representing the 4 receptor sub types and 2 normal
breast cell lines were used in this study. The different cell lines were exposed to incremental FTY720
concentrations and the percentage viability, an indicator of the sensitivity to the drug, was determined
using an MTT cell proliferation assay. Moreover, the expression levels of 33 target genes, including
PP2A activity markers and other breast cancer signature genes, were also evaluated in all breast cancer
cell lines across the various FTY720 concentrations using a multiplex gene expression assay.
Results: A subset of triple negative breast cancer (TNBC) cell lines (namely MDA-MB-231, BT -20,
MDA-MB-468 and HCC1937) was particularly sensitive to FTY720, even at low concentrations. An
evident downregulation of GP2A, a PP2A negative regulator, at mRNA level was observed in MDAMB-
231 and BT -20. Moreover, downregulation of A URKA and KlF2C, 2 genes involved in mitotic
processes, was most evidently observed in MDA-MB-231. Downregulation of these 3 genes also
correlated with cellular viability in the sensitive TNBC cell lines.
Conclusion: The use of FTY720 at low concentrations was effective in reducing the cellular viability
in a subset of cell lines representing the TNBC group, a subtype associated with a poor prognosis and
for which there is no molecularly-targeted therapy. Reduced cellular proliferation seems to be, at least
in part, possibly due to downregulation of CIP2A in MDA-MB-231 and BT -20 and also possibly due to
downregulation of AURKA and KlF2C in MDA-MB-231.
Description: M.SC.BIOMED.SCI.2016-01-01T00:00:00Z