Novel gene C17orf37 in 17q12 amplicon promotes migration and invasion of prostate cancer cells.
C17orf37/MGC14832, a novel gene located on human chromosome 17q12 in the ERBB2 amplicon, is abundantly expressed in breast cancer. C17orf37 expression has been reported to positively correlate with grade and stage of cancer progression; however the functional significance of C17orf37 overexpression in cancer biology is not known. Here, we show that C17orf37 is highly expressed in prostate cancer cell lines and tumors, compared to minimal expression in normal prostate cells and tissues. Cellular localization studies by confocal and total internal reflection fluorescence microscopy revealed predominant expression of C17orf37 in the cytosol with intense staining in the membrane of prostate cancer cells. RNA-interference-mediated downregulation of C17orf37 resulted in decreased migration and invasion of DU-145 prostate cancer cells, and suppressed the DNA-binding activity of nuclear factor-kappaB (NF-kappaB) transcription factor resulting in reduced expression of downstream target genes matrix metalloproteinase 9, urokinase plasminogen activator and vascular endothelial growth factor. Phosphorylation of PKB/Akt was also reduced upon C17orf37 downregulation, suggesting C17orf37 acts as a signaling molecule that increases invasive potential of prostate cancer cells by NF-kappaB-mediated downstream target genes. Our data strongly suggest C17orf37 overexpression in prostate cancer functionally enhances migration and invasion of tumor cells, and is an important target for cancer therapy.
Dasgupta
S
S
Department of Biomedical Sciences and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Wasson
L M
LM
Rauniyar
N
N
Prokai
L
L
Borejdo
J
J
Vishwanatha
J K
JK
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005784:Gene Amplification; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C517054:MIEN1 protein, human; C508053:ERBB2 protein, human