Makhtar, Noor Fatmawati
(2016)
The role of hypoxia in controlling Volatagegated
Sodium Channels (VGSCS) induced breast
cancer invasiveness.
Project Report.
Pusat Pengajian Sains Kesihatan, Universiti Sains Malaysia.
(Submitted)
Abstract
This study was designed mainly to investigate the role of transcription factor, hypoxia inducible factor-
1a (HIF -1a) in enhancing Nav1.5 and nNav1.5 expression in breast cancer that transforms it to
become aggressive. siRNA was conducted to knockdown HIF -1 a expression in the aggressive MDAMB-
231 cells whilst hypoxia-mimetic agent. cobalt chloride (CoCI 2) was used to stabilize HIF-1a in the
less aggressive MCF-7 cells . Total RNA and protein were extracted and subjected to real-time PCR
and Western blotting . Migration and motility assays were carried out to study effect of treatments
(siRNA and CoCI2) on metastatic cell behaviours. Nav1 .5 , nNav1 .5, HIF-1a and CA9 expression were
all hiqhlv expressed in MDA-MB-231 cells . siRNA caused a siqnificant decreased in HIF -1 a expression (mRNA and protein) and HIF-1 a-common target gene. CA9. mRNA expression of Nav1 .5
but not nNav1.5 was significantly downregulated by siRNA-HIF-1a followed by suppression of
migration. When MCF-7 cells were treated with CoCI2 , HIF-1a protein, CA9 and Nav1.5mRNA
expression was increased significantly but not nNav1 .5 followed by enhanced motility and migration.
In conclusion. transcription factor, HIF-1a able to regulate Nav1 .5 (but not nNav1.5) in breast cancer
to promote its aggressiveness.
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