PMID- 15472893
OWN - NLM
STAT- MEDLINE
DCOM- 20050119
LR  - 20161124
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 113
IP  - 4
DP  - 2005 Feb 10
TI  - Multidrug resistance-associated protein (MRP1) is overexpressed in DNA aneuploid 
      carcinomatous cells in non-small cell lung cancer (NSCLC).
PG  - 568-74
AB  - Resistance to chemotherapy is intrinsically present in most nonsmall-cell lung 
      carcinomas (NSCLC). No parameter has yet been determined to predict the response 
      to chemotherapy. However, MRP1 (multidrug resistance-associated protein) is 
      suspected to play an important role in resistance to treatment. The genetic basis 
      for this resistance is not clearly understood, but it could result from 
      chromosome reassortments catalyzed by aneuploidy. The aim of this study was to 
      investigate MRP1 expression concurrently to DNA ploidy analysis in order to 
      evaluate the link between MRP1 expression and chromosome 16 (MRP1 gene location) 
      aberrations in NSCLC before treatment. Eighty-four surgical tumor specimens, 18 
      selected samples containing more than 80% of carcinomatous cells and 11 samples 
      from normal bronchial epithelium were studied. Samples were stained by MRP1 FITC 
      indirect staining and propidium iodide and analyzed by Flow Cytometry. Fifty 
      tumors contained at least 1 DNA-aneuploid clone and the percentage of 
      MRP1-positive cells was higher in DNA-aneuploid cells (p = 0.0003). All tumors 
      expressed MRP1, but the level of expression was 3-fold higher in DNA-aneuploid 
      cells than in DNA-diploid cells (normal bronchial cells as well as carcinomatous 
      cells) (p < 0.0001). FISH analysis of 24 tumor imprints using a chromosome 16 
      alpha-satellite centromere probe demonstrated significantly more frequent gain of 
      chromosome 16 in DNA-aneuploid tumors. These results suggest that MRP1 
      overexpression in NSCLC could be a consequence of chromosome 16 reassortments 
      catalyzed by aneuploidy and that DNA-aneuploid tumors could require different 
      treatment modalities from those applied to DNA-diploid tumors.
FAU - Doubre, Helene
AU  - Doubre H
AD  - Service d'Histologie et Biologie Tumorale, Hopital Tenon (AP-HP), and UPRES 3499, 
      Universite Paris VI, France.
FAU - Cesari, Daniele
AU  - Cesari D
FAU - Mairovitz, Alexa
AU  - Mairovitz A
FAU - Benac, Cecile
AU  - Benac C
FAU - Chantot-Bastaraud, Sandra
AU  - Chantot-Bastaraud S
FAU - Dagnon, Koami
AU  - Dagnon K
FAU - Antoine, Martine
AU  - Antoine M
FAU - Danel, Claire
AU  - Danel C
FAU - Bernaudin, Jean-Francois
AU  - Bernaudin JF
FAU - Fleury-Feith, Jocelyne
AU  - Fleury-Feith J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (DNA, Neoplasm)
RN  - 0 (DNA, Satellite)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - *Aneuploidy
MH  - Bronchi/metabolism
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/*metabolism
MH  - Case-Control Studies
MH  - Centromere/genetics
MH  - Chromosome Aberrations
MH  - Chromosomes, Human, Pair 16/genetics
MH  - DNA, Neoplasm/*genetics
MH  - DNA, Satellite/genetics
MH  - Diploidy
MH  - Drug Resistance, Multiple
MH  - Epithelium/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Lung Neoplasms/*genetics/*metabolism
MH  - Multidrug Resistance-Associated Proteins/*metabolism
EDAT- 2004/10/09 09:00
MHDA- 2005/01/20 09:00
CRDT- 2004/10/09 09:00
PHST- 2004/10/09 09:00 [pubmed]
PHST- 2005/01/20 09:00 [medline]
PHST- 2004/10/09 09:00 [entrez]
AID - 10.1002/ijc.20617 [doi]
PST - ppublish
SO  - Int J Cancer. 2005 Feb 10;113(4):568-74. doi: 10.1002/ijc.20617.