The major vault protein is related to the toxic anion resistance protein (TelA) family

Cellular drug resistance is related to a poor prognosis in childhood leukemia, but little is known about the underlying mechanisms. We studied the expression of P-glycoprotein (P-gp), multidrug resistance (MDR)-associated protein (MRP), and major vault protein/lung resistance protein (LRP) in 141 children with acute lymphoblastic leukemia (ALL) and 27 with acute myeloid leukemia (AML) by flow cytometry. The expression was compared between different types of leukemia and was studied in relation with clinical risk indicators and in vitro cytotoxicity of the MDR-related drugs daunorubicin (DNR), vincristine (VCR), and etoposide (VP16) and the non–MDR-related drugs prednisolone (PRD) and L-asparaginase (ASP). In ALL, P-gp, MRP, and LRP expression did not differ between 112 initial and 29 unrelated relapse samples nor between paired initial and relapse samples from 9 patients. In multiple relapse samples, LRP expression was 1.6-fold higher compared with both initial (P = .026) and first relapse samples (P = .050), which was not observed for P-gp and MRP. LRP expression was weakly but significantly related to in vitro resistance to DNR (Spearman's rank correlation coefficient 0.25, P = .016) but not to VCR, VP16, PRD, and ASP. No significant correlations were found between P-gp or MRP expression and in vitro drug resistance. Samples with a marked expression of two or three resistance proteins did not show increased resistance to the tested drugs compared with the remaining samples. The expression of P-gp, MRP, and LRP was not higher in initial ALL patients with prognostically unfavorable immunophenotype, white blood cell count, or age. The expression of P-gp and MRP in 20 initial AML samples did not differ or was even lower compared with 112 initial ALL samples. However, LRP expression was twofold higher in the AML samples (P < .001), which are more resistant to a variety of drugs compared with ALL samples. In conclusion, P-gp and MRP are unlikely to be involved in drug resistance in childhood leukemia. LRP might contribute to drug resistance but only in specific subsets of children with leukemia.

Download Full-text

Relationship between the intracellular daunorubicin concentration, expression of major vault protein/lung resistance protein and resistance to anthracyclines in childhood acute lymphoblastic leukemia

Leukemia ◽

10.1038/sj.leu.2401576 ◽

1999 ◽

Vol 13 (12) ◽

pp. 2023-2030 ◽

Cited By ~ 23

Author(s):

ML Den Boer ◽

R Pieters ◽

KM Kazemier ◽

GE Janka-Schaub ◽

G Henze ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Childhood Acute Lymphoblastic Leukemia ◽

Major Vault Protein ◽

Lung Resistance Protein ◽

Lung Resistance ◽

Resistance Protein

Download Full-text

Vascular colocalization of P-glycoprotein, multidrug-resistance associated protein 1, breast cancer resistance protein and major vault protein in human epileptogenic pathologies

Neuropathology and Applied Neurobiology ◽

10.1111/j.1365-2990.2005.00699.x ◽

2006 ◽

Vol 32 (1) ◽

pp. 51-63 ◽

Cited By ~ 53

Author(s):

S. M. Sisodiya ◽

L. Martinian ◽

G. L. Scheffer ◽

P. van der Valk ◽

R. J. Scheper ◽

...

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Breast Cancer Resistance Protein ◽

Major Vault Protein ◽

Cancer Resistance ◽

P Glycoprotein ◽

Resistance Protein

Download Full-text

Relationship Between Major Vault Protein/Lung Resistance Protein, Multidrug Resistance-Associated Protein, P-Glycoprotein Expression, and Drug Resistance in Childhood Leukemia

Blood ◽

10.1182/blood.v91.6.2092 ◽

1998 ◽

Vol 91 (6) ◽

pp. 2092-2098 ◽

Cited By ~ 5

Author(s):

M.L. den Boer ◽

R. Pieters ◽

K.M. Kazemier ◽

M.M.A. Rottier ◽

C.M. Zwaan ◽

...

Keyword(s):

Drug Resistance ◽

Multidrug Resistance ◽

Childhood Leukemia ◽

Lymphoblastic Leukemia ◽

Major Vault Protein ◽

Lung Resistance Protein ◽

P Glycoprotein ◽

Lung Resistance ◽

Resistance Protein

Abstract Cellular drug resistance is related to a poor prognosis in childhood leukemia, but little is known about the underlying mechanisms. We studied the expression of P-glycoprotein (P-gp), multidrug resistance (MDR)-associated protein (MRP), and major vault protein/lung resistance protein (LRP) in 141 children with acute lymphoblastic leukemia (ALL) and 27 with acute myeloid leukemia (AML) by flow cytometry. The expression was compared between different types of leukemia and was studied in relation with clinical risk indicators and in vitro cytotoxicity of the MDR-related drugs daunorubicin (DNR), vincristine (VCR), and etoposide (VP16) and the non–MDR-related drugs prednisolone (PRD) and L-asparaginase (ASP). In ALL, P-gp, MRP, and LRP expression did not differ between 112 initial and 29 unrelated relapse samples nor between paired initial and relapse samples from 9 patients. In multiple relapse samples, LRP expression was 1.6-fold higher compared with both initial (P = .026) and first relapse samples (P = .050), which was not observed for P-gp and MRP. LRP expression was weakly but significantly related to in vitro resistance to DNR (Spearman's rank correlation coefficient 0.25, P = .016) but not to VCR, VP16, PRD, and ASP. No significant correlations were found between P-gp or MRP expression and in vitro drug resistance. Samples with a marked expression of two or three resistance proteins did not show increased resistance to the tested drugs compared with the remaining samples. The expression of P-gp, MRP, and LRP was not higher in initial ALL patients with prognostically unfavorable immunophenotype, white blood cell count, or age. The expression of P-gp and MRP in 20 initial AML samples did not differ or was even lower compared with 112 initial ALL samples. However, LRP expression was twofold higher in the AML samples (P < .001), which are more resistant to a variety of drugs compared with ALL samples. In conclusion, P-gp and MRP are unlikely to be involved in drug resistance in childhood leukemia. LRP might contribute to drug resistance but only in specific subsets of children with leukemia.

Download Full-text

Stromal cells extracted from ovarian cancer express functional multi drugs resistance proteins: ATP bindig casset and Major vault protein

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.2072 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 2072-2072

Author(s):

A. Rafii ◽

P. Mirshahi ◽

A. Simon ◽

A. Faussat ◽

E. Ducros ◽

...

Keyword(s):

Flow Cytometry ◽

Ovarian Carcinoma ◽

Stromal Cells ◽

Major Vault Protein ◽

Cancer Resistance ◽

Rt Pcr ◽

Resistance Proteins ◽

Lung Resistance Protein ◽

Resistance Protein ◽

Related Proteins

2072 Background: Stromal cells play a central role for the growth of tumor cells. The functional contribution of these cells in cancer therapy is poorly understood. Here we studied the presenceofthe proteins ABC (ATP binding Cassette) and MVP (Major vault protein) implicated in the multi drugs resistance (MDR) phenomena in stromal cells isolated from ascitis of patients with ovarian carcinoma. Methods: Stromal cells were extracted from ascitis of patients with ovarian carcinoma. The expression of MDR proteins as p-gp (Permeability-glycoprotein), BCRP (breast cancer resistance protein) and MRPs (multidrug related proteins) as well as LRP (lung resistance protein that is a MVP) was studied by two different technique (immunocytochemistry and flow cytometry) using specific antibodies against these proteins. The functionality of the pumps or efflux, was studied by incorporation of fluorescent probes, Rhodamine 123 and JC1, substrate for p-gp, calcéine-AM substrate for p-gp and MRPs and at last Mitoxantrone substratum of BCRP, in the presence of specific inhibitors: as the cyclosporine HAS, the GG918 and the MK571 for the pumps Pgp, BCRP and MRPs respectively. Then the expression of the genes was assessed by RT-PCR. Results: 1) The expression of the proteins ABC is confirmed by immunocytochemistry and by flow cytometry. The Pgp and LRP proteins were strongly expressed and they are functional, the MRP-1, 2, 3 and BCRP proteins are weakly expressed and the MRP-5 protein is not detected. 2) The RNAm corresponding to all of these proteins is found by RT-PCR in the stromal cells. Conclusions: All of these results suggest that the MDR proteins are present on the cells surface of the tumour cell microenvironnement. The functionality of these proteins allows supposing their implication in the phenomena of multi drugs resistance to chemotherapy. The interaction between cancer cells and stromal cells should be targeted during specific chemotherapy. No significant financial relationships to disclose.

Download Full-text