Co-expression of MDR-associated markers, including P-170, MRP and LRP and cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma cell line, OAW42

Morán, Elizabeth; Cleary, Irene; Larkin, Annemarie; Amhlaoibh, R. Nic; Masterson, Allan J.; Scheper, R.J.; Izquierdo, Miguel; O’Sullivan, Finbarr; Clynes, Martin

doi:10.1016/s0959-8049(96)00501-1

Cited by 34 publications

(32 citation statements)

References 21 publications

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“…Although overexpression of LRP/MVP is, in general, paralleled by an increase in drug resistance, in OAW42-S ovarian carcinoma cells an augment in LRP/MVP expression in later passages of these cells did not result in an increase in drug resistance suggesting the presence of a non-functional form of LRP/MVP (Moran, 1997).…”

Section: The Lrp/mvp-associated Phenotype Of Drug Resistance In Vitromentioning

confidence: 87%

“…Overexpression of LRP/MVP has been found in a large number of drug-selected MDR cell lines of various histogenetic origins and selected by different drugs (Moran, 1997;Scheper, 1993;Verovski, 1996), indicating that diverse cancer cells react by up-regulating the expression of the LRP gene after exposure to anti-cancer agents. Overexpression of LRP/MVP is not only seen in highly resistant MDR cell lines, but it is also frequently observed at the early steps of resistance selection (Moran 1997;Verovski, 1996;Versantvoort, 1995;Wyler, 1997).…”

Section: Frequent Overexpression Of Lrp/mvp In Drug-selected and Drugmentioning

confidence: 99%

“…Overexpression of LRP/MVP is not only seen in highly resistant MDR cell lines, but it is also frequently observed at the early steps of resistance selection (Moran 1997;Verovski, 1996;Versantvoort, 1995;Wyler, 1997). The mechanism(s) of drug resistance operative in these LRP/MVP-overexpressing MDR sublines displaying low levels of drug resistance are probably more clinically relevant, pointing to LRP/MVP as a potential useful marker of clinical resistance.…”

Section: Frequent Overexpression Of Lrp/mvp In Drug-selected and Drugmentioning

confidence: 99%

“…This finding points to LRP/MVP, as opposite to Pgp, as a marker of low levels of drug resistance which probably are more clinically relevant. Concomitant overexpression of LRP/MVP and Pgp has been found in few MDR cell lines, such as MCF7/D40 breast cancer cells, OAW42-SR ovarian carcinoma cells, and certain 8226 myeloma sublines (Moran, 1997;. Although most drug-unselected cancer cell lines from the NCI panel expressed LRP/MVP but not Pgp, coexpression of both MDR-related proteins was also seen (Izquierdo 1996b).…”

Section: Lrp/mvp Expression Related To Pgp and Mrp Expressionmentioning

confidence: 99%

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Vault-related resistance to anticancer drugs determined by the expression of the major vault protein LRP

Izquierdo

Scheffer

Schroeijers

et al. 1998

Multiple Drug Resistance in Cancer 2

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Section: The Lrp/mvp-associated Phenotype Of Drug Resistance In Vitromentioning

confidence: 87%

Section: Frequent Overexpression Of Lrp/mvp In Drug-selected and Drugmentioning

confidence: 99%

Section: Frequent Overexpression Of Lrp/mvp In Drug-selected and Drugmentioning

confidence: 99%

Section: Lrp/mvp Expression Related To Pgp and Mrp Expressionmentioning

confidence: 99%

See 2 more Smart Citations

Vault-related resistance to anticancer drugs determined by the expression of the major vault protein LRP

Izquierdo

Scheffer

Schroeijers

et al. 1998

Multiple Drug Resistance in Cancer 2

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“…Involvement of ATP-binding cassette transporters and differential compartmentalization of drugs have been reported to cause resistance to doxorubicin and other drugs in different cell lines (5,19,20). Therefore, to overcome doxorubicin resistance efficacy of glutathione, depletors (21) and inhibitors (22,23) of efflux pumps were studied as resistance-modifying agents for induction of apoptosis of resistant cells with doxorubicin.…”

mentioning

confidence: 99%

Overcoming Drug-Resistant Cancer by a Newly Developed Copper Chelate through Host-Protective Cytokine-Mediated Apoptosis

Mookerjee

Basu

Dutta

et al. 2006

Clinical Cancer Research

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Purpose: Previously, we have synthesized and characterized a novel Cu(II) complex, copper N-(2-hydroxy acetophenone) glycinate (CuNG). Herein, we have determined the efficacy of CuNG in overcoming multidrug-resistant cancer using drug-resistant murine and human cancer cell lines. Experimental Design: Action of CuNG following single i.m. administration (5 mg/kg body weight) was tested in vivo on doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)b earing mice and doxorubicin-resistant sarcoma 180^bearing mice. Tumor size, ascitic load, and survival rates were monitored at regular intervals. Apoptosis of cancer cells was determined by cell cycle analysis, confocal microscopy, Annexin V binding, and terminal deoxynucleotidyl transferase^mediated dUTP nick end labeling assay ex vivo. IFN-g and tumor necrosis factor-a were assayed in the culture supernatants of in vivo and in vitro CuNG-treated splenic mononuclear cells from EAC/Dox-bearing mice and their apoptogenic effect was determined. Source of IFN-g and changes in number of T regulatory marker-bearing cells in the tumor site following CuNG treatment were investigated by flow cytometry. Supernatants of in vitro CuNG-treated cultures of peripheral blood mononuclear cells from different drug-insensitive cancer patients were tested for presence of the apoptogenic cytokine IFN-g and its involvement in induction of apoptosis of doxorubicin-resistant CEM/ADR5000 cells. Results: CuNG treatment could resolve drug-resistant cancers through induction of apoptogenic cytokines, such as IFN-g and/or tumor necrosis factor-a, from splenic mononuclear cells or patient peripheral blood mononuclear cells and reduce the number of Tregulatory marker-bearing cells while increase infiltration of IFN-g-producingTcells in the ascetic tumor site. Conclusion: Our results show the potential usefulness of CuNG in immunotherapy of drugresistant cancers irrespective of multidrug resistance phenotype.

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Intracellular P-glycoprotein expression is associated with the intrinsic multidrug resistance phenotype in human colon adenocarcinoma cells

et al. 2000

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The 2 clones, LoVo 5 and LoVo 7, derived from untreated LoVo WT human colon adenocarcinoma cells and exhibiting different sensitivity to doxorubicin (DOX), were compared in order to identify possible determinants of intrinsic drug resistance. A multidrug resistant variant cell line, selected from LoVo WT cells by continuous exposure to DOX (LoVo DX), was also included in the study. Analysis of the expression and organization of cytoskeletal elements by flow cytometry and fluorescence microscopy evidenced a positive correlation between vimentin expression and DOX resistance in LoVo 7 and LoVo DX cells, whereas differences in actin, tubulin or cytokeratin did not seem to relate to drug response. The expression and localization of different drug transporters commonly implicated in drug resistance, i.e., the MDR1 gene product P‐glycoprotein (P‐gp), the multidrug resistance‐related protein MRP and the lung resistance‐related protein LRP were also investigated by means of flow cytometry and fluorescence microscopy, following labeling with specific monoclonal antibodies. Surface expression of P‐gp was only detected in LoVo DX cells, which also exhibited increased MRP and LRP protein levels. However, significant amounts of P‐gp were found at intracellular sites in the intrinsically resistant LoVo 7 clone. Modulation of P‐gp function by cyclosporin A was found to alter DOX accumulation and efflux in LoVo 7 cells, indicating that intracellular P‐gp plays a functional role in drug trafficking and suggesting possible implications in determining the intrinsic resistance displayed by this clone. Int. J. Cancer 87:615–628, 2000. © 2000 Wiley‐Liss, Inc.

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Co-expression of MDR-associated markers, including P-170, MRP and LRP and cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma cell line, OAW42

Cited by 34 publications

References 21 publications

Vault-related resistance to anticancer drugs determined by the expression of the major vault protein LRP

Vault-related resistance to anticancer drugs determined by the expression of the major vault protein LRP

Overcoming Drug-Resistant Cancer by a Newly Developed Copper Chelate through Host-Protective Cytokine-Mediated Apoptosis

Intracellular P-glycoprotein expression is associated with the intrinsic multidrug resistance phenotype in human colon adenocarcinoma cells

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