Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells

Anke Wichert; Alexandra Stege; Yutaka Midorikawa; Per Sonne Holm; Hermann Lage

doi:10.1038/sj.onc.1207237

Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells

Anke Wichert, Alexandra Stege, Yutaka Midorikawa, Per Sonne Holm, Hermann Lage

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Elevated expression of the heparan sulphate proteoglycan glypican-3 (GPC3) was found on mRNA and protein levels in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV, which was established by in vitro selection against mitoxantrone. In order to elucidate a putative role of GPC3 in the drug-resistant phenotype, the mitoxantrone-resistant cell line EPG85-257RNOV was transfected with an expression vector construct carrying an anti-GPC3 hammerhead ribozyme. It could be demonstrated that in anti-GPC3 ribozyme-transfected cell clones, the GPC3-specific mRNA and corresponding protein expression levels were decreased to levels that are similar to those observed in nonresistant, parental cells. The anti-GPC3 ribozyme-containing clones reduced the mitoxantrone resistance level up to 21% of the original resistance and the crossresistance against etoposide to 33% of the original value. This reversal of drug resistance was accompanied by an increased cellular mitoxantrone accumulation in the anti-GPC3 ribozyme-expressing cells. In conclusion, it was verified that GPC3 is involved in the cellular protection against mitoxantrone in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV.

Original language	English
Pages (from-to)	945-955
Number of pages	11
Journal	Oncogene
Volume	23
Issue number	4
DOIs	https://doi.org/10.1038/sj.onc.1207237
State	Published - 29 Jan 2004
Externally published	Yes

Keywords

Drug resistance
Gastric carcinoma
Glypicans
Mitoxantrone
Ribozymes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/sj.onc.1207237

Cite this

@article{6a64e5434e37449793d148ae54852268,

title = "Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells",

abstract = "Elevated expression of the heparan sulphate proteoglycan glypican-3 (GPC3) was found on mRNA and protein levels in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV, which was established by in vitro selection against mitoxantrone. In order to elucidate a putative role of GPC3 in the drug-resistant phenotype, the mitoxantrone-resistant cell line EPG85-257RNOV was transfected with an expression vector construct carrying an anti-GPC3 hammerhead ribozyme. It could be demonstrated that in anti-GPC3 ribozyme-transfected cell clones, the GPC3-specific mRNA and corresponding protein expression levels were decreased to levels that are similar to those observed in nonresistant, parental cells. The anti-GPC3 ribozyme-containing clones reduced the mitoxantrone resistance level up to 21% of the original resistance and the crossresistance against etoposide to 33% of the original value. This reversal of drug resistance was accompanied by an increased cellular mitoxantrone accumulation in the anti-GPC3 ribozyme-expressing cells. In conclusion, it was verified that GPC3 is involved in the cellular protection against mitoxantrone in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV.",

keywords = "Drug resistance, Gastric carcinoma, Glypicans, Mitoxantrone, Ribozymes",

author = "Anke Wichert and Alexandra Stege and Yutaka Midorikawa and Holm, {Per Sonne} and Hermann Lage",

note = "Funding Information: This work was supported by a grant from the Deutsche Krebshilfe (10-1313-La 3). We thank Yutaka Midorikawa, Hiroyuki Aburatani and Hiroko Iwanari for providing us with the anti-GPC3 mAb K6534.",

year = "2004",

month = jan,

day = "29",

doi = "10.1038/sj.onc.1207237",

language = "English",

volume = "23",

pages = "945--955",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Springer Nature",

number = "4",

}

TY - JOUR

T1 - Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells

AU - Wichert, Anke

AU - Stege, Alexandra

AU - Midorikawa, Yutaka

AU - Holm, Per Sonne

AU - Lage, Hermann

N1 - Funding Information: This work was supported by a grant from the Deutsche Krebshilfe (10-1313-La 3). We thank Yutaka Midorikawa, Hiroyuki Aburatani and Hiroko Iwanari for providing us with the anti-GPC3 mAb K6534.

PY - 2004/1/29

Y1 - 2004/1/29

N2 - Elevated expression of the heparan sulphate proteoglycan glypican-3 (GPC3) was found on mRNA and protein levels in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV, which was established by in vitro selection against mitoxantrone. In order to elucidate a putative role of GPC3 in the drug-resistant phenotype, the mitoxantrone-resistant cell line EPG85-257RNOV was transfected with an expression vector construct carrying an anti-GPC3 hammerhead ribozyme. It could be demonstrated that in anti-GPC3 ribozyme-transfected cell clones, the GPC3-specific mRNA and corresponding protein expression levels were decreased to levels that are similar to those observed in nonresistant, parental cells. The anti-GPC3 ribozyme-containing clones reduced the mitoxantrone resistance level up to 21% of the original resistance and the crossresistance against etoposide to 33% of the original value. This reversal of drug resistance was accompanied by an increased cellular mitoxantrone accumulation in the anti-GPC3 ribozyme-expressing cells. In conclusion, it was verified that GPC3 is involved in the cellular protection against mitoxantrone in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV.

AB - Elevated expression of the heparan sulphate proteoglycan glypican-3 (GPC3) was found on mRNA and protein levels in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV, which was established by in vitro selection against mitoxantrone. In order to elucidate a putative role of GPC3 in the drug-resistant phenotype, the mitoxantrone-resistant cell line EPG85-257RNOV was transfected with an expression vector construct carrying an anti-GPC3 hammerhead ribozyme. It could be demonstrated that in anti-GPC3 ribozyme-transfected cell clones, the GPC3-specific mRNA and corresponding protein expression levels were decreased to levels that are similar to those observed in nonresistant, parental cells. The anti-GPC3 ribozyme-containing clones reduced the mitoxantrone resistance level up to 21% of the original resistance and the crossresistance against etoposide to 33% of the original value. This reversal of drug resistance was accompanied by an increased cellular mitoxantrone accumulation in the anti-GPC3 ribozyme-expressing cells. In conclusion, it was verified that GPC3 is involved in the cellular protection against mitoxantrone in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV.

KW - Drug resistance

KW - Gastric carcinoma

KW - Glypicans

KW - Mitoxantrone

KW - Ribozymes

UR - http://www.scopus.com/inward/record.url?scp=1142267655&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1207237

DO - 10.1038/sj.onc.1207237

M3 - Article

C2 - 14661052

AN - SCOPUS:1142267655

SN - 0950-9232

VL - 23

SP - 945

EP - 955

JO - Oncogene

JF - Oncogene

IS - 4

ER -

Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this