| Summary: | 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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