Abstract
Whilst radioiodine ablation is an effective therapy for many patients
with thyroid cancer, a subset of patients are incapable of accumulating the amount of iodide-131 required for treatment, due to low sodium iodide symporter (NIS) activity. Previous work has identified
that the overexpression of pituitary tumor transforming gene (PTTG)
binding factor (PBF) in thyroid cells leads to the redistribution of NIS
from the plasma membrane into intracellular vesicles, thereby reducing radioiodine uptake. With radioiodine being proposed as a
potential treatment for breast carcinomas, where PBF has been reported to be overexpressed, it is important to discern the relationship
between PBF and NIS in breast cancer cell-lines.
Immunofluorescent microscopy was used to image MCF-7 and
T47D cells to evaluate subcellular localisation of transfected NIS-MYC
and PBF-HA. NIS activity was assessed in MCF-7 and MDA-MB-231
cells by measuring the uptake of Iodine-125.
Immunofluorescent microscopy revealed co-localisation between
NIS and PBF in transfected MCF-7 and T47D cells, with increased
intracellular staining for NIS compared to cells transfected with NIS
alone. We have recently identified PBF as a tyrosine phosphorylated
protein, with phosphorylation at residue Y174 critical to NIS regulation in thyroid cells. Importantly, phosphorylated PBF co-localised at
the plasma membrane with NIS in T47D breast cells. In preliminary
functional studies MCF-7 cells, PBF repressed radioiodine uptake in
cells that had been transfected with NIS (Fold change = 0.12), as well
as those treated with the NIS-inducing reagents all-trans retinoic acid
(ATRA) and dexamethasone (Fold Change = 0.38). PBF also significantly repressed iodide uptake in MDA-MB-231 cells transfected with
NIS (fold change = 0.75, p < 0.05).
Taken together, these data suggest that PBF can alter the subcellular location of NIS and thereby reduce the ability of breast carcinoma cell-lines to take up iodide, consistent with those findings
previously reported in thyroid cells.
with thyroid cancer, a subset of patients are incapable of accumulating the amount of iodide-131 required for treatment, due to low sodium iodide symporter (NIS) activity. Previous work has identified
that the overexpression of pituitary tumor transforming gene (PTTG)
binding factor (PBF) in thyroid cells leads to the redistribution of NIS
from the plasma membrane into intracellular vesicles, thereby reducing radioiodine uptake. With radioiodine being proposed as a
potential treatment for breast carcinomas, where PBF has been reported to be overexpressed, it is important to discern the relationship
between PBF and NIS in breast cancer cell-lines.
Immunofluorescent microscopy was used to image MCF-7 and
T47D cells to evaluate subcellular localisation of transfected NIS-MYC
and PBF-HA. NIS activity was assessed in MCF-7 and MDA-MB-231
cells by measuring the uptake of Iodine-125.
Immunofluorescent microscopy revealed co-localisation between
NIS and PBF in transfected MCF-7 and T47D cells, with increased
intracellular staining for NIS compared to cells transfected with NIS
alone. We have recently identified PBF as a tyrosine phosphorylated
protein, with phosphorylation at residue Y174 critical to NIS regulation in thyroid cells. Importantly, phosphorylated PBF co-localised at
the plasma membrane with NIS in T47D breast cells. In preliminary
functional studies MCF-7 cells, PBF repressed radioiodine uptake in
cells that had been transfected with NIS (Fold change = 0.12), as well
as those treated with the NIS-inducing reagents all-trans retinoic acid
(ATRA) and dexamethasone (Fold Change = 0.38). PBF also significantly repressed iodide uptake in MDA-MB-231 cells transfected with
NIS (fold change = 0.75, p < 0.05).
Taken together, these data suggest that PBF can alter the subcellular location of NIS and thereby reduce the ability of breast carcinoma cell-lines to take up iodide, consistent with those findings
previously reported in thyroid cells.
| Original language | English |
|---|---|
| Article number | P30 |
| Journal | Thyroid |
| Volume | 23(1_Suppl) |
| Publication status | Published - 2013 |
| Event | 83rd Annual Meeting of the American Thyroid Association - San Juan, Puerto Rico Duration: 16 Oct 2013 → 20 Oct 2013 |
