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VDAC1 and SERCA3 Mediate Progesterone-Triggered Ca2+ Signaling in Breast Cancer Cells
journal contribution
posted on 2017-11-29, 00:00 authored by Juberiya
M. Azeez, Ravindran Vini, Viji Remadevi, Arun Surendran, Abdul Jaleel, T. R. Santhosh Kumar, S. SreejaProgesterone is a biphasic
hormone whose confounding role in breast cancer cells involves an
initial proliferative surge, followed by sustained growth arrest.
Recently we reported that progesterone induces a time- and concentration-dependent
release of reactive oxygen species and thus regulates the antiproliferative
activity in the breast cancer cell line. Furthermore, the expression
of p27, a crucial cell cycle control protein, was regulated by binding
of progesterone on progesterone receptor B, thus leading to antiproliferative
signaling via multiple signaling pathways including p53, PTEN, and
antioxidant systems. Here, we performed an LC–MS/MS analysis of three
different breast cancer cell lines. Bioinformatics data analysis and
functional classification of proteins revealed a role of progesterone
in calcium signaling in MCF-7 cells, and the major differentially
expressed calcium regulators were S100A11, S100A10, calreticulin,
VDAC1, SERCA3, and SERCA1. Later on we confirmed it by a cell-line-based
system having a calcium cameleon sensor targeted at endoplasmic reticulum
and found moderate calcium efflux from endoplasmic reticulum upon
progesterone treatment. Real-time PCR, Western blot, and TMRM staining
confirmed the role of calcium signaling regulators
VDAC1 and SERCA3 in progesterone response. Taking together all of
these results with our previous studies, we suggest that progesterone,
by regulating important proteins involved in calcium signaling and
transport, can modulate cell proliferation and cell death. Furthermore,
our research may open new avenues for the hypothesis that surgery
conducted during the luteal phase of the menstrual cycle might facilitate
improved patient survival.
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breast cancer cell lineTMRMBioinformatics data analysisBreast Cancer Cells ProgesteronePCRprogesterone receptor Bregulators VDAC 1reactive oxygen speciesSERCA 3 Mediate Progesterone-TriggeredMCF -7 cellsbreast cancer cellsendoplasmic reticulumcell cycle control proteinbreast cancer cell linesS 100A S 100A calreticulincalcium cameleon sensorLCrolePTEN
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