Expression of multidrug resistance-associated protein (MRP), MDR1 and DNA topoisomerase II in human multidrug-resistant bladder cancer cell lines

Hasegawa, Shuji; Abe, Tetsutaro; Naito, Seiji; Kotoh, Shuji; Kumazawa, Joichi; Hipfner, David R.; Deeley, Roger G.; Cole, Susan P. C.; Kuwano, Michihiko

doi:10.1038/bjc.1995.177

Cited by 77 publications

(44 citation statements)

References 22 publications

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“…In the present study, the extent of topoisomerase I mRNA expression was similar in the multidrug-resistant sublines and the parental cell lines, which did not reflect the differences in sensitivity to CPT-1 1 and SN-38. Consistent with our finding, the expression of the topoisomerase I gene in the multidrug-resistant KK47/ADM and T24NVCR human bladder cancer sublines was similar to that in the parental cell lines, although there was an approximately threefold resistance against CPT-1 1 (Hasegawa et al, 1995).…”

Section: Discussionsupporting

confidence: 89%

“…Cross-resistance against carboxylesterase-activated CPT-11 and SN-38 was observed in GLC4/ADR cells, whereas in the SW1573/Sl(MRP) cells crossresistance was not evident. Hasegawa et al (1995) have demonstrated that T24/ADM-1 and T24/ADM-2 human bladder cancer cells, both overexpressing the MRP gene, were not cross-resistant against CPT-11, whereas the cells showed cross-resistance against doxorubicin and etoposide. Thus, it is probable that CPT-1 1 is not a substrate for MRP and the cross-resistance in the GLC4/ADR subline might be related to other factors of relevance for sensitivity to CPT-l 1.…”

Section: Discussionmentioning

confidence: 99%

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CPT-11 sensitivity in relation to the expression of P170-glycoprotein and multidrug resistance-associated protein

Jansen

Hulscher²,

Ark-Otte³

et al. 1998

Br J Cancer

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Summary The relevance of P170-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) for the sensitivity to CPT-11 was investigated in human malignant cell lines as well as in human tumour xenografts. In vitro, the P-gp-positive sublines BRO/mdrl.1 (transfected with MDR1) and 2780AD were slightly cross-resistant against carboxylesterase-activated CPT-11. Cross-resistance against SN-38 was present in 2780AD cells, but not in BRO/mdrl.1 cells. The P-gp modulators BIBW22BS, verapamil and dexniguldipine partly reversed the resistance against CPT-11 in the P-gp-positive sublines. BIBW22BS was the most effective modulator in the reversal of the resistance against carboxylesterase-activated CPT-11 as well as against in the 2780AD subline. In contrast to doxorubicin and vincristine, the BRO/mdrl.1 xenografts were at least as sensitive to CPT-11 as the BRO xenografts. The 2780AD xenografts were slightly less sensitive than the parent tumours, but there was no difference in topoisomerase I DNA unwinding activity. Therefore, the high retention of the multidrugresistant phenotype of 2780AD cells in vivo may be the cause of the low cross-resistance against CPT-11. The MRP-positive subline GLC4/ADR was cross-resistant against carboxylesterase-activated CPT-11 and SN-38. GLC4/ADR cells, however, demonstrated a twofold lower topoisomerase I activity than GLC4 cells. Cross-resistance against the camptothecin derivatives was not apparent in the MRPtransfected subline of SW1573/Si. In conclusion, P-gp-positive cells show a low cross-resistance against CPT-11/SN38, which is only apparent with high P-gp expression in vivo. MRP does not seem to play a role in the sensitivity to

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

CPT-11 sensitivity in relation to the expression of P170-glycoprotein and multidrug resistance-associated protein

Jansen

Hulscher²,

Ark-Otte³

et al. 1998

Br J Cancer

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“…T24 cells line, established from a high grade and invasive human urinary bladder cancer patient and usually used as a model for drug sensitivity studies [21], was kindly supplied by Shanghai Institute of Cell Biology, Chinese Academy of Sciences. The cells were maintained in RPMI 1640 (GIBCO-BRL), supplemented with 5% heat-inactivated fetal calf serum (FCS), 1% Lglutamine, 1% penicillin/streptomycin solution, which contained 10,000 U/ml penicillin G and 10 mg/ml streptomycin sulfate.…”

Section: Cells Culturementioning

confidence: 99%

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Sun

Shu

2001

Cell Res

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A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.

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“…(1) reduced topo I catalytic activity (Madelaine et al, 1993;Fujimori et al, 1995;Sorensen et al, 1995), (2) decreased formation of cleavable complexes (Madelaine et al, 1993;Fujimori et al, 1995), (3) decreased expression of topo I (Eng et al, 1990;Sugimoto et al, 1990) and (4) a point mutation or rearrangement of topo I genes (Andoh et al, 1987;Fujimori et al, 1995). Reduced accumulation of TPT, due to P-glycoprotein (Pgp) overexpression, has been reported to add to resistance to topo I inhibitors as well Mattern et al, 1993;Hasegawa et al, 1995). Moreover, TPT is also a substrate for the multidrug resistance-associated protein (MRP) (Maliepaard et al, 1996).…”

mentioning

confidence: 99%

Reduced cellular accumulation of topotecan: a novel mechanism of resistance in a human ovarian cancer cell line

Maliepaard²,

Nooter³

et al. 1998

Br J Cancer

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Summary In order to unravel possible mechanisms of clinical resistance to topoisomerase inhibitors, we developed a topotecan-resistant human IGROV-1 ovarian cancer cell line, denoted IGROVTlOOr, by stepwise increased exposure to topotecan (TPT). The IGROVT100r cell line was 29-fold resistant to TPT and strongly cross-resistant to . However, the IGROVTlOOr showed only threefold resistance to camptothecin (CPT). Remarkably, this cell line was 32-fold resistant to mitoxantrone, whereas no significant cross-resistance against other cytostatic drugs was observed. No differences in topoisomerase protein levels and catalytic activity as well as topoisomerase cleavable complex stabilization by CPT in the IGROV-1 and IGROVTIOOr cell lines were observed, indicating that resistance in the IGROVTlOOr cell line was not related to topoisomerase I-related changes. However, resistance in the resistant IGROVTlOOr cell line to accompanied by decreased accumulation of the drugs to approximately 15% and 36% of that obtained in IGROV-1 respectively. No reduced accumulation was observed for CPT. Notably, accumulation of TPT in the IGROV-1 cell line decreased under energy-deprived conditions, whereas the accumulation in the IGROVTlOOr cell line increased under these energy-deprived conditions. The efflux of TPT at 370C was very rapid in the IGROV-1 as well as the IGROVT100r cell line, resulting in 90% efflux within 20 min. Importantly, the efflux rates of TPT in the IGROV-1 and IGROVTlOOr cell lines were not significantly different and were shown to be independent on P-glycoprotein (P-gp) or multidrug resistance-associated protein (MRP). These results strongly suggest that the resistance of the IGROVTlOOr cell line to TPT and SN-38 is mainly caused by reduced accumulation. The reduced accumulation appears to be mediated by a novel mechanism, probably related to impaired energy-dependent uptake of these topoisomerase drugs.

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Expression of multidrug resistance-associated protein (MRP), MDR1 and DNA topoisomerase II in human multidrug-resistant bladder cancer cell lines

Cited by 77 publications

References 22 publications

CPT-11 sensitivity in relation to the expression of P170-glycoprotein and multidrug resistance-associated protein

CPT-11 sensitivity in relation to the expression of P170-glycoprotein and multidrug resistance-associated protein

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Reduced cellular accumulation of topotecan: a novel mechanism of resistance in a human ovarian cancer cell line

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