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Neonatal Nav1.5 protein expression in normal adult human tissues and breast cancer

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dc.contributor.authorKAYA, HANDAN
dc.contributor.authorsYamaci, Rezan Fahrioglu; Fraser, Scott P.; Battaloglu, Esra; Kaya, Handan; Erguler, Kamil; Foster, Christopher S.; Djamgoz, Mustafa B. A.
dc.date.accessioned2022-03-12T22:24:09Z
dc.date.available2022-03-12T22:24:09Z
dc.date.issued2017
dc.description.abstractExpression of the neonatal splice variant of the voltage-gated sodium channel alpha-subunit (VGSC) subtype Nav1.5 (nNav1.5), encoded by the gene SCN5A, was shown earlier to be upregulated in human breast cancer (BCa), both in vitro and in vivo. Channel activity promoted BCa invasion of Matrigel (R) in vitro and metastasis in vivo. Consequently, expression of nNav1.5 has been proposed as a functional biomarker of BCa cells with metastatic potential. Here, we have determined immunohistochemically both nNav1.5 and total VGSC (tVGSC) protein expression in a range of adult human tissues. Some VGSC protein was expressed in normal colon, small intestine, stomach, prostate, bladder and breast. As expected, high levels of VGSC protein were expressed in brain, skeletal muscle and cardiac muscle. On the other hand, nNav1.5 protein was not expressed in any of the normal tissues tested except breast where a low-level of protein was present. In comparison to normal breast, nNav1.5 protein expression in BCa was consistently widespread and occurred at a significantly higher level. We also questioned whether there was any relationship between the nNav1.5 protein expression and the estrogen receptor (ER alpha) status of BCa and obtained the following results. First, all cases lacking nNav1.5 were positive for ERa. SOecond, in all ER alpha-negative tissues, nNav1.5 protein was expressed in plasma membrane. Third, however, in ER alpha-positive cases, nNav1.5 protein expression was observed in both plasma membrane and cytoplasm. In conclusion, nNav1.5 protein has a restricted expression pattern among human tissues. High level expression occurs in BCa and associates with ERa status. These results further support the proposition that nNav1.5 is a novel biomarker of metastatic BCa. (C) 2017 Elsevier GmbH. All rights reserved.
dc.identifier.doi10.1016/j.prp.2017.06.003
dc.identifier.issn0344-0338
dc.identifier.pubmed28698102
dc.identifier.urihttps://hdl.handle.net/11424/234687
dc.identifier.wosWOS:000407410300006
dc.language.isoeng
dc.publisherELSEVIER GMBH
dc.relation.ispartofPATHOLOGY RESEARCH AND PRACTICE
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectBreast cancer
dc.subjectMetastasis
dc.subjectVoltage-gated sodium channel
dc.subjectNeonatal Nav1.5
dc.subjectEstrogen receptor
dc.subjectGATED SODIUM-CHANNELS
dc.subjectHUMAN PROSTATE-CANCER
dc.subjectFUNCTIONAL EXPRESSION
dc.subjectESTROGEN-RECEPTOR
dc.subjectTUMOR GROWTH
dc.subjectINVASION
dc.subjectCOLON
dc.subjectDISSEMINATION
dc.subjectINVASIVENESS
dc.subjectPOTENTIATION
dc.titleNeonatal Nav1.5 protein expression in normal adult human tissues and breast cancer
dc.typearticle
dspace.entity.typePublication
local.avesis.id14739db7-573d-4221-8089-9b18efa29711
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages8
local.journal.quartileQ3
oaire.citation.endPage907
oaire.citation.issue8
oaire.citation.startPage900
oaire.citation.titlePATHOLOGY RESEARCH AND PRACTICE
oaire.citation.volume213
relation.isAuthorOfPublication0bf301ff-2544-4a5e-b38b-b43084d6c255
relation.isAuthorOfPublication.latestForDiscovery0bf301ff-2544-4a5e-b38b-b43084d6c255

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