Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues

Dingemans, Anne Marie C.; Ark-Otte, J. van; Valk, Paul van der; Apolinario, Rosa María Cáceres; Scheper, Rik J.; Postmus, P.E.; Giaccone, Giuseppe

doi:10.1093/oxfordjournals.annonc.a010681

Cited by 50 publications

(40 citation statements)

References 16 publications

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“…These data are in accord with the expression of LRP mRNA as shown in Table 3. In agreement with the finding of Dingemans et al, 29) there was no significant correlation between LRP expression and chemosensitivity in the three NSCLC cell lines, suggesting that LRP is not involved in the chemoresistance of these NSCLC cells.…”

Section: Chemosensitivity Of Nsclc Cell Lines To Anticancer Drugssupporting

confidence: 92%

Expression of Multidrug Resistance Proteins and Accumulation of Cisplatin in Human Non-small Cell Lung Cancer Cells

Ikuta

Takemura

Sasaki

et al. 2005

Biological & Pharmaceutical Bulletin

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Lung cancer is currently the leading cause of cancer deaths worldwide. Primary lung cancers are classified into two main histological groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC constitutes approximately 85% of all lung cancers and often shows intrinsic multidrug resistance (MDR), whereas SCLC almost always responds well to various anticancer agents. 1) Cisplatin is an established antitumor agent for the treatment of advanced human NSCLC and is employed in cisplatin-based adjuvant chemotherapy. 2,3) Although the development of resistance to cisplatin is one of the major obstacles in the successful treatment of NSCLC, the molecular mechanisms involved remain poorly understood. In order to overcome the problems related to drug resistance and to improve the clinical outcome of patients with NSCLC, the mechanisms of cancer chemoresistance must be more clearly elucidated.Our previous in vitro study using three NSCLC cell lines has demonstrated that cisplatin has triggered apoptosis more easily in the chemosensitive human NSCLC cell line than the chemoresistant cell line, based on biochemical and morphological findings. 4) We have also reported that an increased transcriptional level of constitutive signal transducer and activator of transcription (STAT) 3 may be related to the suppressive regulation of the apoptotic pathway in intrinsically chemoresistant NSCLC cells. 4)However, multiple factors are involved in the chemoresistance of cancer cells, suggesting that other mechanisms or factors may also contribute to the resistance of the NSCLC cell lines. Therefore, it is needed to further study other cellular mechanisms of chemoresistance, such as ATP-binding cassette transporters and lung resistance-related protein (LRP), important in drug disposition and in the development of MDR, together with measuring the concentration of anticancer agent in cancer cells.During the past decade, there have been many studies linking various transporters to MDR both in cell culture and in the clinical setting. Of these proteins, P-glycoprotein (MDR1), multidrug resistance-associated protein 1 (MRP1), and LRP have attracted considerable attention in studies of cancer chemotherapy. In tumor cell lines, MDR is often associated with overexpression of ATP-dependent drug efflux proteins belonging to the superfamily of ATP-binding cassette transporters: the 170-kDa MDR1 and the 190-kDa MRP1.5) These proteins bind to and transport various structurally unrelated compounds to maintain their intracellular concentrations below cytotoxic levels. In addition to an overall decrease in intracellular drug concentration, redistribution of the drug from the nucleus to the cytoplasm has also been implicated in MDR of cancer cells. 6) Recently, another drug resistance-related protein, referred to as LRP, has been identified.7) LRP has been found to be identical to the human major vault protein, which is the major component of vaults.8) Vaults are mainly located in the cytoplasm, and approximately 5% of cellular va...

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Section: Chemosensitivity Of Nsclc Cell Lines To Anticancer Drugssupporting

confidence: 92%

Expression of Multidrug Resistance Proteins and Accumulation of Cisplatin in Human Non-small Cell Lung Cancer Cells

Ikuta

Takemura

Sasaki

et al. 2005

Biological & Pharmaceutical Bulletin

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“…Most of the studies concerning LRP expression in solid tumors were based on immunohistochemistry using a score evaluation (Dingemans et al 1996;Volm et al 1997) or reverse transcriptionpolymerase chain reaction (RT-PCR) evaluating LRP mRNA (Ohno et al 2001), whereas the majority of studies on hematological malignancies used flow cytometry for LRP detection (Damiani et al 2004). Moreover, this method has not been previously used to compare LRP expression in normal and carcinomatous cells from the same tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Respiratory airway cells continuously exposed to airborne pollutants, particularly genotoxic xenobiotics such as tobacco smoke, like all epithelial cells localized at the interface with the external environment are known to possess well-developed cell detoxification mechanisms, particularly the MDR phenotype (Dingemans et al 1996). We, like others, have already explored the localization of two ABC transporters in airway tissues: P-gp170, a product of the mdr1 gene expressed in normal airways at the apical cell membrane of ciliated cells (Lechapt-Zalcman et al 1997;Wioland et al 2000), whereas MRP1 encoded by the mrp gene is expressed both at the basolateral cell membrane of ciliated and basal cells and at the intracellular level (Brechot et al 1998;Wioland et al 2000).…”

mentioning

confidence: 99%

Immunolocalization and Cell Expression of Lung Resistance-related Protein (LRP) in Normal and Tumoral Human Respiratory Cells

Bouhamyia

Chantot‐Bastaraud

Zaïdi

et al. 2007

J Histochem Cytochem.

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Lung resistance-related protein (LRP) is an integral part of the multidrug resistance (MDR) phenotype involved in cell resistance toward xenobiotics or chemotherapy. The aim of this study was to compare the intracellular localization and cell expression of LRP in normal bronchial cells and their tumoral counterparts from non-small cell lung cancer (NSCLC). LRP expression was also investigated concurrently with DNA ploidy and chromosome 16 ( lrp gene locus) aberrations. Confocal microscopy showed that LRP localization was exclusively intracytoplasmic regardless of the cell type and was never observed in the nuclear pore complex. Flow cytometry demonstrated a similar level of LRP expression in normal bronchial cells and in cancer cells from NSCLC samples. FISH analysis, performed to evaluate the number of chromosome 16 and lrp loci, demonstrated a significant gain of chromosome 16 in DNA aneuploid tumors. Furthermore, we did not find any link between LRP expression and DNA ploidy status or chromosome 16 number. These results suggest that LRP expression observed in NSCLC, maintained through the carcinogenesis process of respiratory cells, is not altered by the increased number of copies of chromosome 16 and probably controlled by mechanisms different from those of MRP1 expression, whereas both proteins are associated with the MDR phenotype. (J Histochem Cytochem 55: 773–782, 2007)

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“…Although treatment of P-Glycoprotein (P-gp) negative Lu-24 SCLC cells with etoposide and vincristine induced expression of P-gp and the MDR1 gene product (Abe et al, 1996), such induction was not found in other cell lines (Supino et al, 1993). Furthermore, clinical studies investigating expression of lung resistance protein (LRP), mdr1 or P-gp in tumour material after chemotherapy demonstrated that expression was rarely induced and did not correlate with the clinical response (Dingemans et al, 1996;Savaraj et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

In vitro chemo- and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways

et al. 2002

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Most small cell lung cancer (SCLC) patients relapse within 12 months of starting combination chemotherapy plus radio-therapy, due to the development of acquired chemo-and radio-resistance. This phenomenon relates to the induction of tumour differentiation, resulting in apoptosis-resistant, morphologically variant (v-SCLC) cells, which lack the neuroendocrine expression of classic (c-) SCLC cells. In this study spontaneously adherent SCLC sublines were shown by differential gene expression analysis to provide an in vitro model of variant differentiation in SCLC, with down-regulation of neuroendocrine markers and up-regulation of epithelial differentiation markers cyclin D1, endothelin, the cell adhesion molecules CD 44 and integrin subunits a2, b3 and b4. The sensitivity of adherent SCLC sublines to etoposide, cyclophosphamide and gamma radiation was significantly diminished relative to parent suspension cell lines. Western blot analysis using phosphorylationspecific antibodies to Akt and MAP kinase revealed markedly elevated activation in adherent SCLC sublines, paralleled by increased levels of phosphorylated Bad protein and activated NF-kB. Subcultivation of the adherent sublines on uncoated surfaces reversed their adherent phenotype immediately and under these conditions Akt activity reverted to low levels. These results suggest that c-SCLC cells can differentiate spontaneously to v-SCLC and that the associated cellular adhesion may trigger Akt-dependent inhibition of apoptosis in SCLC cells, thus leading to acquired chemoand radio-resistance.

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Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues

Cited by 50 publications

References 16 publications

Expression of Multidrug Resistance Proteins and Accumulation of Cisplatin in Human Non-small Cell Lung Cancer Cells

Expression of Multidrug Resistance Proteins and Accumulation of Cisplatin in Human Non-small Cell Lung Cancer Cells

Immunolocalization and Cell Expression of Lung Resistance-related Protein (LRP) in Normal and Tumoral Human Respiratory Cells

In vitro chemo- and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways

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