PMID- 10049829
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20131121
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 255
IP  - 1
DP  - 1999 Mar 1
TI  - Antisense downregulation of a mouse mammary tumor virus activated protooncogene 
      in mouse mammary tumor cells reverses the malignant phenotype.
PG  - 138-49
AB  - Activation of the protooncogene Wnt-1 by insertion of the mouse mammary tumor 
      virus (MMTV) is known to cause mammary tumors in mice. Wnt-1 expression in 
      mammary glands has been postulated to confer direct local growth stimulation of 
      mammary epithelial cells leading to their acquisition of a preneoplastic state. 
      Wnt-1 expression also induces morphological alterations in cultured normal 
      mammary cells. However, it has not been determined whether or not transformed 
      mammary cells require continuous Wnt-1 expression for their ability to form 
      tumors in vivo. To address this question, we constructed antisense and sense 
      Wnt-1 expression vectors containing a synthetic promoter composed of five 
      high-affinity glucocorticoid response elements (GRE5). This promoter is at least 
      50-fold more inducible by dexamethasone than the promoter contained in the long 
      terminal repeats of MMTV. The vectors were introduced into a mouse mammary tumor 
      cell line (R/Sa-MT) that expresses high levels of endogenous Wnt-1 mRNA and forms 
      rapidly growing tumors when transplanted into syngeneic hosts. Of the 12 stably 
      transfected cell lines established (9 with antisense and 3 with sense 
      constructs), 2 antisense cell lines (R/Sa-MT/antisense) and 1 sense cell line 
      (R/Sa-MT/sense) were examined for inducibility by dexamethasone of antisense and 
      sense Wnt-1 RNAs, changes in endogenous Wnt-1 RNA expression, and changes in cell 
      morphology. The growth patterns of the cells in vitro and in vivo were also 
      examined. Our results show that (1) the levels of the expression of endogenous 
      Wnt-1 mRNA and protein were reduced significantly (>80%) in those cells 
      (R/Sa-MT/antisense) that expressed antisense Wnt-1 RNA at high levels following 
      exposure to dexamethasone, compared to the R/Sa-MT/sense and R/Sa-MT control 
      cells and (2) transplantation of the R/Sa-MT/antisense cells produced smaller 
      tumors ( approximately 0.2 cm in 16 weeks) compared to the tumors ( approximately 
      2.0 cm in 8 weeks) that were produced by the R/Sa-MT/sense and R/Sa-MT cells. We 
      therefore suggest that Wnt-1 expression is required not only for the 
      transformation of normal mammary cells into tumor cells, but also for the 
      maintenance of their tumorigenicity.
CI  - Copyright 1999 Academic Press.
FAU - Li, Y X
AU  - Li YX
AD  - Institute of Molecular Medicine and Genetics, Medical College of Georgia, 
      Augusta, Georgia 30912, USA.
FAU - Papkoff, J
AU  - Papkoff J
FAU - Sarkar, N H
AU  - Sarkar NH
LA  - eng
GR  - 7 F05 TW04695-02/TW/FIC 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  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Glucocorticoids)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt1 Protein)
RN  - 0 (Wnt1 protein, mouse)
RN  - 0 (Zebrafish Proteins)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Cell Division
MH  - Dexamethasone/metabolism/pharmacology
MH  - *Down-Regulation
MH  - Glucocorticoids/metabolism/pharmacology
MH  - Mammary Tumor Virus, Mouse/*genetics
MH  - Mice
MH  - Neoplasms, Experimental
MH  - Phenotype
MH  - Proto-Oncogene Proteins/*genetics
MH  - *Proto-Oncogenes
MH  - *RNA, Antisense
MH  - RNA, Messenger
MH  - Tumor Cells, Cultured
MH  - Wnt Proteins
MH  - Wnt1 Protein
MH  - *Zebrafish Proteins
EDAT- 1999/03/02 00:00
MHDA- 1999/03/02 00:01
CRDT- 1999/03/02 00:00
PHST- 1999/03/02 00:00 [pubmed]
PHST- 1999/03/02 00:01 [medline]
PHST- 1999/03/02 00:00 [entrez]
AID - S0042-6822(98)99571-X [pii]
AID - 10.1006/viro.1998.9571 [doi]
PST - ppublish
SO  - Virology. 1999 Mar 1;255(1):138-49. doi: 10.1006/viro.1998.9571.