Silencing of the SEC62 gene inhibits migratory and invasive potential of various tumor cells.
Sec62 is part of the protein translocation apparatus in the membrane of the endoplasmic reticulum (ER). In yeast, Sec62 participates in the post-translational translocation of proteins into the ER, but its function in mammals remains elusive. Previously we described the amplification and over-expression of the SEC62 gene in prostate cancer cell lines and the protein has been described as a potential target gene in prostate cancer. In the current study we show that in the tumor tissue of prostate cancer patients Sec62 protein levels are elevated compared with tumor-free tissue derived from the same patients or from prostates of control group patients and that the higher Sec62 protein content correlates with an increasing de-differentiation of the cells. Therefore, up-regulation of Sec62 protein content indeed is a phenomenon associated with prostate cancer progression. Analysis of a multi-tissue tumor array showed that in addition to prostate cancer, overproduction of Sec62 is observed in various other tumors, most significantly in tumors of the lung and the thyroid. To examine the tumor-related functions of Sec62, we silenced the SEC62 gene in the prostate cancer cell-line PC3 as well as in a set of other tumor cell-lines with two different siRNAs. In general, after silencing of SEC62 the cell migration and the invasive potential of the cells was blocked or at least dramatically reduced while cell viability was hardly affected. Thus, the SEC62 gene may indeed be considered as a target gene in the therapy of various tumors.
Greiner
Markus
M
Department of Medical Biochemistry and Molecular Biology, Saarland University, Homburg/Saar, Germany. bcmgrei@uks.eu
Kreutzer
Birgit
B
Jung
Volker
V
Grobholz
Rainer
R
Hasenfus
Andrea
A
Stöhr
Robert Franz
RF
Tornillo
Luigi
L
Dudek
Johanna
J
Stöckle
Michael
M
Unteregger
Gerhard
G
Kamradt
Jörn
J
Wullich
Bernd
B
Zimmermann
Richard
R
D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering
D026901:Membrane Transport Proteins; D034741:RNA, Small Interfering; C103676:SEC62 protein, human