title: A novel role of myosin VI in human prostate cancer.
abstract: Myosin VI is an actin motor that moves to the minus end of the polarized actin filament, a direction opposite to all other characterized myosins. Using expression microarrays, we identified myosin VI as one of the top genes that demonstrated cancer-specific overexpression in clinical prostate specimens. Protein expression of myosin VI was subsequently analyzed in arrayed prostate tissues from 240 patients. Notably, medium-grade prostate cancers demonstrated the most consistent cancer-specific myosin VI protein overexpression, whereas prostate cancers associated with more aggressive histological features continued to overexpress myosin VI but to a lesser extent. Myosin VI protein expression in cell lines positively correlated with the presence of androgen receptor. Small interference RNA-mediated myosin VI knockdown in the LNCaP human prostate cancer cell line resulted in impaired in vitro migration and soft-agar colony formation. Depletion of myosin VI expression was also accompanied by global gene expression changes reflective of attenuated tumorigenic potential, as marked by a nearly 10-fold induction of TXNIP (VDUP1), a tumor suppressor with decreased expression in prostate cancer specimens. These results support that myosin VI is critical in maintaining the malignant properties of the majority of human prostate cancers diagnosed today.
authors.affiliation: Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Dunn
authors.forename: Shenglin
authors.initials: S
authors.lastname: Chen
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Faith
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hicks
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.forename: Charles M
authors.initials: CM
authors.lastname: Ewing
authors.forename: Jurga
authors.initials: J
authors.lastname: Sauvageot
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
mesh_terms: D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D012333:RNA, Messenger; C486715:TXNIP protein, human; C089785:myosin VI; D013879:Thioredoxins; D018995:Myosin Heavy Chains