A novel role of myosin VI in human prostate cancer.
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.
Dunn
Thomas A
TA
Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Chen
Shenglin
S
Faith
Dennis A
DA
Hicks
Jessica L
JL
Platz
Elizabeth A
EA
Chen
Yidong
Y
Ewing
Charles M
CM
Sauvageot
Jurga
J
Isaacs
William B
WB
De Marzo
Angelo M
AM
Luo
Jun
J
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
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D012333:RNA, Messenger; C486715:TXNIP protein, human; C089785:myosin VI; D013879:Thioredoxins; D018995:Myosin Heavy Chains