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

Abstract

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)

Vaults and the major vault protein: Novel roles in signal pathway regulation and immunity

“…Additionally, it must be mentioned that several proteins encoded by very important (proto)oncogenes (EGF/EGFR, Src, cJun), but also tumor-suppressor genes (e.g. PTEN, [35,36,136] or maintain the high MVP expression already present in the respective normal tissues [117,118,157]. Accordingly, in some tumor types MVP levels correlated with a worse prognosis not related to chemotherapy failure [37].…”

“…Vaults are frequently expressed in tissues chronically exposed to the environment and consequently prone to get in contact with xenobiotics, including the epithelia of lung and digestive tract as well as early stages of embryonic development [62,117,118]. In addition to the distinct correlation of intrinsic drug resistance with MVP expression in several human malignancies in vitro and in vivo [16,34], MVP is almost generally overexpressed in drug resistant human cancer cells selected against a wide array of chemotherapeutic drugs [29,33,55,119].…”

Reversal of multidrug resistance by cisplatin-loaded magnetic Fe3O4 nanoparticles in A549/DDP lung cancer cells in vitro and in vivo

“…These results suggest that the regulatory mechanism of both LRP and MRP1 expression is associated with the multidrug resistance phenotype. 28 The results of some studies point to the fact that one of the important mechanisms of tumorigenesis and resistance to anticancer drugs is blockade of the pathway triggering apoptosis. 38,39 Understanding of the molecular mechanisms of resistance to DDP may lead to improved treatment strategies for DDP-resistant tumors and increased survival in patients with lung cancer.…”

Up-regulation of major vault protein in the frontal cortex of patients with intractable frontal lobe epilepsy

“…The functional role of overexpression of vaults is still speculative, but it has been proposed to play an important role in drug resistance. Vaults are frequently expressed in tissues chronically exposed to the environment and consequently prone to get in contact with xenobiotics, including the epithelia of lung and digestive tract as well as early stages of embryonic development [3,16,17]. Previous studies showed that MVP is almost generally overexpressed in drug-resistant human cancer cells selected against a wide array of chemotherapeutic drugs [18][19][20][21].…”