PMID- 10070941
OWN - NLM
STAT- MEDLINE
DCOM- 19990317
LR  - 20190513
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 91
IP  - 5
DP  - 1999 Mar 3
TI  - Atypical multidrug resistance: breast cancer resistance protein messenger RNA
      expression in mitoxantrone-selected cell lines.
PG  - 429-33
AB  - BACKGROUND: Human cancer cell lines grown in the presence of the cytotoxic agent 
      mitoxantrone frequently develop resistance associated with a reduction in
      intracellular drug accumulation without increased expression of the known drug
      resistance transporters P-glycoprotein and multidrug resistance protein (also
      known as multidrug resistance-associated protein). Breast cancer resistance
      protein (BCRP) is a recently described adenosine triphosphate-binding cassette
      transporter associated with resistance to mitoxantrone and anthracyclines. This
      study was undertaken to test the prevalence of BCRP overexpression in cell lines 
      selected for growth in the presence of mitoxantrone. METHODS: Total cellular RNA 
      or poly A+ RNA and genomic DNA were isolated from parental and drug-selected cell
      lines. Expression of BCRP messenger RNA (mRNA) and amplification of the BCRP gene
      were analyzed by northern and Southern blot hybridization, respectively. RESULTS:
      A variety of drug-resistant human cancer cell lines derived by selection with
      mitoxantrone markedly overexpressed BCRP mRNA; these cell lines included sublines
      of human breast carcinoma (MCF-7), colon carcinoma (S1 and HT29), gastric
      carcinoma (EPG85-257), fibrosarcoma (EPF86-079), and myeloma (8226) origins.
      Analysis of genomic DNA from BCRP-overexpressing MCF-7/MX cells demonstrated that
      the BCRP gene was also amplified in these cells. CONCLUSIONS: Overexpression of
      BCRP mRNA is frequently observed in multidrug-resistant cell lines selected with 
      mitoxantrone, suggesting that BCRP is likely to be a major cellular defense
      mechanism elicited in response to exposure to this drug. It is likely that BCRP
      is the putative "mitoxantrone transporter" hypothesized to be present in these
      cell lines.
FAU - Ross, D D
AU  - Ross DD
AD  - University of Maryland Greenebaum Cancer Center, Department of Medicine,
      University of Maryland School of Medicine, and Baltimore Veterans Medical Center,
      21201, USA. DROSS@umcc01.umcc.ab.umd.edu
FAU - Yang, W
AU  - Yang W
FAU - Abruzzo, L V
AU  - Abruzzo LV
FAU - Dalton, W S
AU  - Dalton WS
FAU - Schneider, E
AU  - Schneider E
FAU - Lage, H
AU  - Lage H
FAU - Dietel, M
AU  - Dietel M
FAU - Greenberger, L
AU  - Greenberger L
FAU - Cole, S P
AU  - Cole SP
FAU - Doyle, L A
AU  - Doyle LA
LA  - eng
SI  - GENBANK/AF098951
GR  - CA52178/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - BZ114NVM5P (Mitoxantrone)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Blotting, Northern
MH  - Blotting, Southern
MH  - Breast Neoplasms/*drug therapy/genetics/*metabolism
MH  - Colonic Neoplasms/drug therapy/metabolism
MH  - *Drug Resistance, Multiple/genetics
MH  - *Drug Resistance, Neoplasm/genetics
MH  - Fibrosarcoma/drug therapy/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mitoxantrone/*pharmacology
MH  - Multiple Myeloma/drug therapy/metabolism
MH  - Neoplasm Proteins/*biosynthesis/genetics
MH  - RNA, Messenger/analysis
MH  - RNA, Neoplasm/analysis
MH  - Stomach Neoplasms/drug therapy/metabolism
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 1999/03/10 00:00
MHDA- 1999/03/10 00:01
CRDT- 1999/03/10 00:00
PHST- 1999/03/10 00:00 [pubmed]
PHST- 1999/03/10 00:01 [medline]
PHST- 1999/03/10 00:00 [entrez]
AID - 10.1093/jnci/91.5.429 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 1999 Mar 3;91(5):429-33. doi: 10.1093/jnci/91.5.429.