PMID- 1281476
OWN - NLM
STAT- MEDLINE
DCOM- 19930121
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 267
IP  - 36
DP  - 1992 Dec 25
TI  - Human T-cell leukemia virus type I tax transformation is associated with 
      increased uptake of oligodeoxynucleotides in vitro and in vivo.
PG  - 25881-8
AB  - We have utilized antisense oligodeoxynucleotides (ODNs) to modulate 
      transcriptional activation by the human T-cell leukemia virus type I (HTLV-I) tax 
      gene, the major transcriptional regulator of this virus. 3'-Terminal 
      phosphorothioate-modified antisense ODNs were shown to efficiently inhibit Tax 
      protein expression both in vitro and in vivo. Terminal substitution did not 
      affect the affinity of ODNs for their target sequence but conferred a 9-fold 
      increase in tax inhibition in vitro. When delivered into mice by intraperitoneal 
      injection, ODNs inhibited tax expression in established tumors by 90%. 
      Unmanipulated tax-transformed mouse fibroblasts, or HTLV-I-transformed human 
      lymphocytes, showed at least 5-fold higher ODN binding and uptake over control 
      cells. Balb/3T3 cell binding was induced to similar levels by cellular 
      activators. This suggests that constitutive activation by tax transformation may 
      increase susceptibility of HTLV-I-transformed cells to antisense therapy, 
      providing a rationale for the use of antisense ODN therapeutics in 
      HTLV-I-associated diseases.
FAU - Kitajima, I
AU  - Kitajima I
AD  - Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 
      92037.
FAU - Shinohara, T
AU  - Shinohara T
FAU - Minor, T
AU  - Minor T
FAU - Bibbs, L
AU  - Bibbs L
FAU - Bilakovics, J
AU  - Bilakovics J
FAU - Nerenberg, M
AU  - Nerenberg M
LA  - eng
GR  - CA50234/CA/NCI NIH HHS/United States
GR  - MH47680/MH/NIMH NIH HHS/United States
GR  - NS01330/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 63231-63-0 (RNA)
SB  - IM
GS  - tax
MH  - 3T3 Cells
MH  - Animals
MH  - Base Sequence
MH  - Biological Transport
MH  - Blotting, Northern
MH  - Cell Line
MH  - *Cell Transformation, Neoplastic
MH  - Female
MH  - Genes, pX/*drug effects
MH  - Human T-lymphotropic virus 1/*drug effects/*genetics
MH  - Kinetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides/*metabolism/*pharmacology
MH  - Oligonucleotides, Antisense/*metabolism/*pharmacology
MH  - Organ Specificity
MH  - RNA/genetics/isolation & purification
MH  - Repetitive Sequences, Nucleic Acid
MH  - Transcriptional Activation/*drug effects
EDAT- 1992/12/25 00:00
MHDA- 1992/12/25 00:01
CRDT- 1992/12/25 00:00
PHST- 1992/12/25 00:00 [pubmed]
PHST- 1992/12/25 00:01 [medline]
PHST- 1992/12/25 00:00 [entrez]
AID - S0021-9258(18)35691-6 [pii]
PST - ppublish
SO  - J Biol Chem. 1992 Dec 25;267(36):25881-8.