PMID- 8823806
OWN - NLM
STAT- MEDLINE
DCOM- 19961127
LR  - 20171116
IS  - 0965-0407 (Print)
IS  - 0965-0407 (Linking)
VI  - 8
IP  - 3
DP  - 1996
TI  - Transfection of a human topoisomerase II alpha gene into etoposide-resistant 
      human breast tumor cells sensitizes the cells to etoposide.
PG  - 101-10
AB  - The etoposide-resistant human breast cancer cell line MDA-VP was derived from 
      MDA-parent cells by sequential selection in increasing concentrations of 
      etoposide. MDA-VP cells express a lower amount of topoisomerase II alpha mRNA 
      than the MDA-parent does, have mutations in topoisomerase II alpha (topo II) 
      cDNA, and show cross-resistance to doxorubicin and amsacrine. We investigated 
      whether transfer of a normal human topoisomerase II alpha (H-topo II) gene into 
      MDA-VP cells could overcome their resistance to etoposide. H-topo II in a 
      mammalian expression vector containing a glucocorticoid-inducible mouse mammary 
      tumor virus (MMTV) promoter (pMAMneo) was transfected into MDA-VP cells 
      (MDA-VP-hTOP2MAM). These H-topo II-transfected cells showed increased H-topo II 
      mRNA expression and protein levels compared with MDA-VP parental cells or with 
      MDA-VP cells transfected with the control pMAM vector (MDA-VP-MAM). Following 
      cell exposure to dexamethasone, DNA-protein cleavable complex formation and 
      cytotoxicity induced by etoposide, doxorubicin, and amsacrine were increased in 
      the MDA-VP-hTOP2MAM cells compared with MDA-VP-MAM cells. However, these changes 
      were short-lived, and by 24 h, cytotoxicity, cleavable DNA-protein complex 
      formation, and H-topo II protein levels returned to baseline values. These 
      results indicate that sensitivity of MDA-VP cells correlated with changes in 
      cellular H-topo II. The gene transfer of a normal H-topo II gene can sensitize 
      MDA-VP cells to the actions of multiple antineoplastic agents that target topo 
      II.
FAU - Asano, T
AU  - Asano T
AD  - Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, 
      Houston 77030, USA.
FAU - An, T
AU  - An T
FAU - Zwelling, L A
AU  - Zwelling LA
FAU - Takano, H
AU  - Takano H
FAU - Fojo, A T
AU  - Fojo AT
FAU - Kleinerman, E S
AU  - Kleinerman ES
LA  - eng
GR  - CA 16672/CA/NCI NIH HHS/United States
GR  - CA 40090/CA/NCI NIH HHS/United States
GR  - CA 42992/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Oncol Res
JT  - Oncology research
JID - 9208097
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 00DPD30SOY (Amsacrine)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 80168379AG (Doxorubicin)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
SB  - IM
MH  - Amsacrine/administration & dosage
MH  - Animals
MH  - Antigens, Neoplasm/*genetics
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Breast Neoplasms/*drug therapy
MH  - Cell Cycle/genetics
MH  - Cell Death/genetics
MH  - Cell Division/genetics
MH  - *DNA Topoisomerases, Type II/*genetics
MH  - DNA-Binding Proteins
MH  - Doxorubicin/administration & dosage
MH  - Drug Resistance, Multiple/genetics
MH  - Drug Resistance, Neoplasm/genetics
MH  - Etoposide/*pharmacology
MH  - Female
MH  - Humans
MH  - Isoenzymes/*genetics
MH  - Mice
MH  - RNA, Messenger/biosynthesis
MH  - Transfection
MH  - Tumor Cells, Cultured/drug effects
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
PST - ppublish
SO  - Oncol Res. 1996;8(3):101-10.