title: Expression of Voltage-Gated Sodium Channel Nav1.8 in Human Prostate Cancer is Associated with High Histological Grade.
abstract: Voltage-gated sodium (Nav) channels are required for impulse conductance in excitable tissues. Navs have been linked to human cancers, including prostate. The expression and distribution of Navisoforms (Nav1.1-Nav1.9) in human prostate cancer are not well established. Here, we evaluated the expression of these isoforms and investigated the expression of Nav1.8 in human prostate cancer tissues. Nav1.8 was highly expressed in all examined cells. Expression of Nav1.1, Nav1.2, and Nav1.9 were high in DU-145, PC-3 and PC-3M cells compared to LNCaP (hormone-dependent), C4-2, C4-2B, and CWR22Rv-1 cells. Nav1.5 and Nav1.6 were expressed in all cells examined. Nav1.7 expression was absent in PC-3M and CWR22Rv-1, but expressed in the other cells examined. Immunohistochemistry revealed intensive Nav1.8 staining correlated with more advanced pathologic stage of disease. Increased intensity of nuclear Nav1.8 correlated with increased Gleason grade. Our results revealed that Nav1.8 is universally expressed in human prostate cancer cells. Nav1.8 expression statistically correlated with pathologic stage (P=0.04) and Gleason score (P=0.01) of human prostate tissue specimens. The aberrant nuclear localization of Nav1.8 with advanced prostate cancer tissues warrant further investigation into use of Nav1.8 as a potential biomarker to differentiate between early and advanced disease.
authors.affiliation: Drug Discovery Program, Georgetown University Medical Center, Washington DC, USA ; Department of Radiation Medicine, Georgetown University Medical Center, Washington DC, USA.
authors.forename: Simeng
authors.initials: S
authors.lastname: Suy
authors.forename: Todd P
authors.initials: TP
authors.lastname: Hansen
authors.forename: Heather D
authors.initials: HD
authors.lastname: Auto
authors.forename: Bhaskar V S
authors.initials: BV
authors.lastname: Kallakury
authors.forename: Vernon
authors.initials: V
authors.lastname: Dailey
authors.forename: Malika
authors.initials: M
authors.lastname: Danner
authors.forename: Linda
authors.initials: L
authors.lastname: Macarthur
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Miessau
authors.forename: Sean P
authors.initials: SP
authors.lastname: Collins
authors.forename: Milton L
authors.initials: ML
authors.lastname: Brown
keywords: Gleason score; Prostate biomarker; Prostate cancer; Voltage-gated sodium channel