Disease relevance of MVP

• METHODS: Hippocampal sclerosis (HS), focal cortical dysplasia (FCD), and dysembryoplastic neuroepithelial tumor (DNT) were studied by using immunohistochemistry for MVP and BCRP [1].
• Optimal immunocytochemical and flow cytometric detection of P-gp, MRP and LRP in childhood acute lymphoblastic leukemia [2].
• Human T-cell lymphotropic virus type I Tax activates lung resistance-related protein expression in leukemic clones established from an adult T-cell leukemia patient [3].
• The findings indicate that the in vivo expression of LRP, but not of Pgp and MRP-1, is induced by chemotherapeutic treatment in rhabdomyosarcomas [4].
• Recently, a protein overexpressed in a non-PGP MDR lung cancer cell line and termed lung resistance related protein (LRP) was identified [5].

High impact information on MVP

• The LRP gene is located on chromosome 16, close to the genes coding for multidrug resistance-associated protein and protein kinase C-beta, and may mediate drug resistance, perhaps via a transport process [6].
• LRP overexpression has been found to predict a poor response to chemotherapy in acute myeloid leukaemia and ovarian carcinoma [6].
• The deduced LRP amino acid sequence shows 87.7% identity with the 104-kD rat major vault protein [6].
• Multidrug resistance and the lung resistance-related protein in human colon carcinoma SW-620 cells [7].
• METHODS: SW-620 cells, a human colon carcinoma cell line, alone or transfected with an expression vector carrying a LRP-specific ribozyme or with an empty vector, were treated with sodium butyrate to induce differentiation [7].

Chemical compound and disease context of MVP

• Expression of P-glycoprotein, multidrug resistance-associated protein 1, and lung resistance-related protein in human soft tissue sarcomas before and after hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan [8].
• Among the determinants studied in ovarian cancer in vivo, LRP mRNA and the S-phase fraction were the best predictive factors for drug response and most specifically for the activity of cisplatin [9].
• The rhodamine uptake was increased in L5178/MDR1 and Colo320/MDR1-LRP, but not drug-sensitive human breast cancer MCF-7 and T47D, and L5178 mouse lymphoma parent cells in the presence of alis-409 and alis-421 [10].
• To predict response chemotherapy using technetium-99m tetrofosmin chest images in patients with untreated small cell lung cancer and compare with p-glycoprotein, multidrug resistance related protein-1, and lung resistance-related protein expression [11].
• Eighty patients with relapsing/refractory AML were randomly assigned to mitoxantrone (M) and etoposide (VP) (MVP) in unmitigated antileukaemic doses with or without CsA, to investigate if toxicity was manageable and if antileukaemic therapy could be improved [12].

Biological context of MVP

• Therefore, YB-1 is directly linked to MVP-mediated drug resistance [13].
• Ectopic upregulation of MVP was seen in hilar neurons in HS, dysplastic neurons in FCD, and lesional neurons in DNT [1].
• Vaults and MVP have been associated with several cellular processes which are also involved in cancer development like cell motility and differentiation [14].
• Because cells transfected with the LRP gene did not express the multidrug-resistant phenotype, we investigated whether LRP is involved in multidrug resistance [7].
• These data indicate that although both the MRP and LRP genes map to the short arm of chromosome 16, they are rarely coamplified and are not normally located within the same amplicon [15].

Anatomical context of MVP

• RESULTS: MVP and BCRP were expressed ubiquitously in brain capillary endothelium [1].
• Amplification of LRP was not identified in any of seven other drug-resistant tumor cell lines characterized by 20-300-fold levels of doxorubicin resistance, including two cell lines known to overexpress LRP (SW1573/2R120 and GLC4/ADR) [15].
• Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours [16].
• Since no cell line expressing all three antigens is known, we mixed K562 cells (resistant to Adriblastine, PGP+, MRP-, LRP-) with GLC4 cells (resistant to Adriblastine, PGP-, MRP+, LRP+) to create a model system to test the method [5].
• The expression of LRP was detected in the cytoplasm close to the nuclear membrane [17].

Associations of MVP with chemical compounds

• 5-FU also induced reporter expressions driven by a panel of newly generated MVP promoter deletion mutants [13].
• Isolated nuclei from untreated cells or sodium butyrate-treated cells incubated with anti-LRP polyclonal antibodies contained more doxorubicin than the nuclei of sodium butyrate-treated cells alone [7].
• For lung resistance-related protein, this association was limited to 5-fluorouracil, Adriamycin/epirubicin, and cyclophosphamide [18].
• The optimal fixation for P-gp (C219, MRK16), MRP (MRPr1) and LRP (LRP56) was a mixture of 2% (v/v) formaldehyde solution and acetone incubated for only 10 s at room temperature (FAc) [2].
• The results of the present study indicate that resistance in LoVo/C7 cells cannot be attributed to alterations in P-gp, LRP or GSH/GSH-dependent enzyme levels [19].

Physical interactions of MVP

• PTEN reportedly interacts in vitro with the EF hand-like motif of MVP in a Ca(2+)-dependent manner [20].
• However, the N-terminal half of MVP binds to a specific domain in the C-terminus of VPARP [21].
• A novel human zinc finger protein ZNF540 interacts with MVP and inhibits transcriptional activities of the ERK signal pathway [22].

Regulatory relationships of MVP

• Here, we demonstrate that besides MDR-related cytostatics, also the non-MDR-related drug 5-fluorouracil (5-FU) was able to induce MVP mRNA and protein expression [13].
• In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FU-induced MVP promoter activity [13].
• Mutation of this site distinctly reduced basal as well as IFN-gamma-stimulated MVP transcription [23].
• Treatment of the tumor cells with EGF or TGFalpha (25 ng/ml) significantly down-regulated total cellular LRP [24].

Other interactions of MVP

• P-glycoprotein, lung resistance-related protein and multidrug resistance-associated protein in de novo adult acute lymphoblastic leukaemia [25].
• We also summarize recent advances concerning resistance to cancer drug therapies with respect to the function and overexpression of ABC and LRP multidrug transporters [26].
• Major vault protein, a marker of drug resistance, is upregulated in refractory epilepsy [1].
• Positive correlation between TEP1 and LRP also seems to identify them as common targets of IFN-alpha effects [27].
• Using Southern blot analysis, LRP gene amplification was shown not to be associated with LRP overexpression [28].

Analytical, diagnostic and therapeutic context of MVP

• Expression of P-glycoprotein, multidrug resistance protein, and LRP in the cells was examined by northern and western blotting, and the efflux of doxorubicin in the cells or isolated nuclei was examined by fluorescence microscopy [7].
• Dual color fluorescence in situ hybridization studies refined the localization of LRP to 16p11.2, a location approximately 27 cM proximal to MRP (16p13.1) [15].
• RT-PCR demonstrated that MRP1 mRNA was expressed, but MDR1, cMOAT, and LRP mRNAs were not in S1T or S1Tneo [3].
• Despite the increased background in the triple labelling we were able to detect coexpression of PGP, MRP, LRP by flow cytometry [5].
• No differences were found in terms of PGP and LRP expressions between ANLL developing after chemo/radiotherapy (therapy-related ANLL) or evolving from a myelodysplastic syndrome (MDS-related ANLL) [29].

References