start-ver=1.4
cd-journal=joma
no-vol=126
cd-vols=
no-issue=7
article-no=
start-page=1562
end-page=1569
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2010
dt-pub=20100401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Down-regulation of BiP/GRP78 sensitizes resistant prostate cancer cells to gene-therapeutic overexpression of REIC/Dkk-3
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We have recently shown that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) exhibits a potent tumor-specific cell-killing function for various human cancers. It has also become evident that some human cancers are resistant to Ad-REIC-induced apoptosis. The aim of the present study was to determine the molecular mechanisms of resistance to Ad-REIC. First, we isolated resistant clones from a human prostate cancer cell line, PC3, after repeated exposure to Ad-REIC. Infection efficiency of the adenovirus vector and expression level of REIC/Dkk-3 in the resistant clones were similar to those in the parental PC3 cells. By screening for alteration in levels and functional status of proteins involved in Ad-REIC-induced apoptosis, we found that BiP/GRP78, an ER-residing chaperone protein, was expressed at higher levels consistently among resistant cells. Expression levels of BiP and rates of apoptosis induced by Ad-REIC were inversely correlated. Down-regulation of BiP with siRNA sensitized the resistant cells to Ad-REIC in vivo as well as in culture. These results indicate that BiP is a major determinant of resistance to Ad-REIC-induced apoptosis. Thus BiP is useful for diagnosis of inherent and acquired resistance of cancers and also as a target molecule to overcome resistance to the gene therapeutic Ad-REIC.
en-copyright=
kn-copyright=

en-aut-name=TanimotoRyuta
en-aut-sei=Tanimoto
en-aut-mei=Ryuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AbarzuaFernando
en-aut-sei=Abarzua
en-aut-mei=Fernando
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KataokaKen
en-aut-sei=Kataoka
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KuroseKaoru
en-aut-sei=Kurose
en-aut-mei=Kaoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NasuYasutomo
en-aut-sei=Nasu
en-aut-mei=Yasutomo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KumonHiromi
en-aut-sei=Kumon
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HuhNam-Ho
en-aut-sei=Huh
en-aut-mei=Nam-Ho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=6
en-affil=
kn-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=8
en-affil=
kn-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=9
en-affil=
kn-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=REIC
kn-keyword=REIC
en-keyword=Dkk
kn-keyword=Dkk
en-keyword=apoptosis
kn-keyword=apoptosis
en-keyword=GRP78
kn-keyword=GRP78
en-keyword=ER stress
kn-keyword=ER stress
END