Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression
Acquisition of P-gp-mediated multidrug-resistance does not always correlate with observed malignant behavior of NB. To characterize alterations accompanying development of multidrug-resistance in NB we established two neuroblastoma cell sublines resistant to vincristine (UKF-NB-3rVCR10) and doxorubicin (UKF-NB-3rDOX20). UKF-NB-3rVCR10 and UKF-NB-3rDOX20 overexpressed functional P-gp and developed an increased malignant phenotype: presented constitutive phosphorylation of AKT, resistance to gamma-irradiation, and had increased survival in serum-free medium. Inhibition of P-gp restored chemosensitivity but did not affect increased survival in serum-free medium and sensitivity to gamma-irradiation. Inhibition of AKT had no influence on chemoresistance but restored sensitivity to serum starvation. Both resistant cell lines acquired additional chromosomal changes. UKF-NB-3rVCR10 cells acquired a missense P53 mutation in exon 5, an increased MYCN amplification, an enhanced adhesion to endothelium, a decreased NCAM expression, a distinctly higher clonogenicity, and an increased in vivo tumorigenicity. We conclude that acquisition of increased malignant behavior in neuroblastoma occurs concomitantly with multidrug-resistance and is P-gp-independent.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2005 |
|---|---|
| Erschienen: |
2005 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
|---|---|
| Enthalten in: |
International journal of oncology - 27(2005), 4 vom: 29. Okt., Seite 1029-37 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kotchetkov, Rouslan [VerfasserIn] |
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| Anmerkungen: |
Date Completed 31.01.2006 Date Revised 01.12.2018 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM157591034 |
|---|
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| 008 | 231223s2005 xx ||||| 00| ||eng c | ||
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| 035 | |a (NLM)16142320 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kotchetkov, Rouslan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression |
| 264 | 1 | |c 2005 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 31.01.2006 | ||
| 500 | |a Date Revised 01.12.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Acquisition of P-gp-mediated multidrug-resistance does not always correlate with observed malignant behavior of NB. To characterize alterations accompanying development of multidrug-resistance in NB we established two neuroblastoma cell sublines resistant to vincristine (UKF-NB-3rVCR10) and doxorubicin (UKF-NB-3rDOX20). UKF-NB-3rVCR10 and UKF-NB-3rDOX20 overexpressed functional P-gp and developed an increased malignant phenotype: presented constitutive phosphorylation of AKT, resistance to gamma-irradiation, and had increased survival in serum-free medium. Inhibition of P-gp restored chemosensitivity but did not affect increased survival in serum-free medium and sensitivity to gamma-irradiation. Inhibition of AKT had no influence on chemoresistance but restored sensitivity to serum starvation. Both resistant cell lines acquired additional chromosomal changes. UKF-NB-3rVCR10 cells acquired a missense P53 mutation in exon 5, an increased MYCN amplification, an enhanced adhesion to endothelium, a decreased NCAM expression, a distinctly higher clonogenicity, and an increased in vivo tumorigenicity. We conclude that acquisition of increased malignant behavior in neuroblastoma occurs concomitantly with multidrug-resistance and is P-gp-independent | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a ATP Binding Cassette Transporter, Subfamily B, Member 1 |2 NLM | |
| 650 | 7 | |a Antibiotics, Antineoplastic |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents, Phytogenic |2 NLM | |
| 650 | 7 | |a Culture Media, Serum-Free |2 NLM | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 650 | 7 | |a Rhodamine 123 |2 NLM | |
| 650 | 7 | |a 1N3CZ14C5O |2 NLM | |
| 650 | 7 | |a Vincristine |2 NLM | |
| 650 | 7 | |a 5J49Q6B70F |2 NLM | |
| 650 | 7 | |a Doxorubicin |2 NLM | |
| 650 | 7 | |a 80168379AG |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Driever, Pablo Hernáiz |e verfasserin |4 aut | |
| 700 | 1 | |a Cinatl, Jaroslav |e verfasserin |4 aut | |
| 700 | 1 | |a Michaelis, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Karaskova, Jana |e verfasserin |4 aut | |
| 700 | 1 | |a Blaheta, Roman |e verfasserin |4 aut | |
| 700 | 1 | |a Squire, Jeremy A |e verfasserin |4 aut | |
| 700 | 1 | |a Von Deimling, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Moog, Jussi |e verfasserin |4 aut | |
| 700 | 1 | |a Cinatl, Jindrich |c Jr |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:27 |g year:2005 |g number:4 |g day:29 |g month:10 |g pages:1029-37 |
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| 952 | |d 27 |j 2005 |e 4 |b 29 |c 10 |h 1029-37 | ||