PMID- 16489039
OWN - NLM
STAT- MEDLINE
DCOM- 20060413
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 4
DP  - 2006 Feb 15
TI  - Cell adhesion to fibronectin (CAM-DR) influences acquired mitoxantrone resistance 
      in U937 cells.
PG  - 2338-45
AB  - Cell adhesion to fibronectin is known to confer a temporally related cell 
      adhesion-mediated drug resistance (CAM-DR). However, it is unknown whether cell 
      adhesion during drug selection influences the more permanent form of acquired 
      drug resistance. To examine this question, we compared the acquisition of 
      mitoxantrone resistance in U937 cells adhered to fibronectin versus cells 
      selected in a traditional suspension culture. Our data show that acquired drug 
      resistance levels of resistance to mitoxantrone are 2- to 3-fold greater for 
      cells adhered to fibronectin compared with cells in suspension culture. We also 
      compared mechanism(s) of resistance associated with drug selection in suspension 
      versus fibronectin-adherent cultures. Drug resistance in both suspension and 
      fibronectin-adhered cultures correlated with reduced drug-induced DNA damage and 
      diminished topoisomerase II levels and activity; however, mechanisms regulating 
      topoisomerase II levels differed depending on culture conditions. In suspension 
      cultures, a reduction in topoisomerase IIbeta levels was detected at both RNA and 
      protein levels. Furthermore, the decreased expression of topoisomerase IIbeta 
      mRNA levels correlated with decreased expression of NF-YA. In contrast, in spite 
      of no changes in NF-YA or topoisomerase IIbeta RNA expression, topoisomerase 
      IIbeta protein levels were decreased in fibronectin-adherent, drug-resistant 
      cells. In addition, topoisomerase IIalpha protein levels (but not RNA levels) 
      were reduced in drug resistance cells selected on fibronectin; however, no change 
      in topoisomerase IIalpha was observed in cells selected with mitoxantrone in 
      suspension culture. Taken together, our results suggest that the development of 
      drug resistance models must consider interactions with the microenvironment to 
      identify clinically relevant targets and mechanisms associated with acquired drug 
      resistance.
FAU - Hazlehurst, Lori A
AU  - Hazlehurst LA
AD  - Department of Interdisciplinary Oncology and Experimental Therapeutics Program, 
      H. Lee Moffitt Cancer Center and Research Institute at the University of South 
      Florida, Tampa, Florida 33613, USA.
FAU - Argilagos, Raul F
AU  - Argilagos RF
FAU - Emmons, Michael
AU  - Emmons M
FAU - Boulware, David
AU  - Boulware D
FAU - Beam, Craig A
AU  - Beam CA
FAU - Sullivan, Dan M
AU  - Sullivan DM
FAU - Dalton, William S
AU  - Dalton WS
LA  - eng
GR  - CA76292/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (FANCE protein, human)
RN  - 0 (Fanconi Anemia Complementation Group E Protein)
RN  - 0 (Fibronectins)
RN  - BZ114NVM5P (Mitoxantrone)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
RN  - Q41OR9510P (Melphalan)
SB  - IM
MH  - Cell Adhesion/physiology
MH  - DNA Damage
MH  - DNA Topoisomerases, Type II/metabolism
MH  - Drug Resistance, Neoplasm
MH  - Fanconi Anemia Complementation Group E Protein/biosynthesis
MH  - Fibronectins
MH  - Gene Expression Profiling
MH  - Humans
MH  - Lymphoma, Large B-Cell, Diffuse/*drug therapy/genetics/metabolism/*pathology
MH  - Melphalan/pharmacokinetics/pharmacology
MH  - Mitoxantrone/pharmacokinetics/*pharmacology
MH  - Oligonucleotide Array Sequence Analysis
MH  - U937 Cells
EDAT- 2006/02/21 09:00
MHDA- 2006/04/14 09:00
CRDT- 2006/02/21 09:00
PHST- 2006/02/21 09:00 [pubmed]
PHST- 2006/04/14 09:00 [medline]
PHST- 2006/02/21 09:00 [entrez]
AID - 66/4/2338 [pii]
AID - 10.1158/0008-5472.CAN-05-3256 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Feb 15;66(4):2338-45. doi: 10.1158/0008-5472.CAN-05-3256.