PMID- 9040938
OWN - NLM
STAT- MEDLINE
DCOM- 19970506
LR  - 20151119
IS  - 1044-9523 (Print)
IS  - 1044-9523 (Linking)
VI  - 8
IP  - 2
DP  - 1997 Feb
TI  - Inactivation of retinoblastoma family proteins by SV40 T antigen results in 
      creation of a hepatocyte growth factor/scatter factor autocrine loop associated 
      with an epithelial-fibroblastoid conversion and invasiveness.
PG  - 165-78
AB  - SV40 T antigen (LT) is an oncoprotein that inactivates nuclear regulators such as 
      retinoblastoma (RB) family proteins and p53. We recently reported that in 
      Madin-Darby canine kidney (MDCK) epithelial cells the binding of LT to RB family 
      proteins results in a massive apoptosis and a concomitant down-regulation of 
      c-myc. Here, we show that LT causes loss of epithelial differentiation and 
      induces invasiveness. MDCK cells expressing wild-type LT, but not mutants unable 
      to bind RB, exhibit a fibroblast-like morphology, show a strong down-regulation 
      of the vHNF1 transcription factor and acquire invasive properties. The stable 
      retransformation of MDCK(LT) with a RB and/or c-myc-expressing vector restores 
      the expression of epithelial characteristics. Our data therefore suggest an 
      important role for RB and c-myc in modulating the epithelial phenotype both 
      during normal tissue development and in invasive processes. In addition, when 
      grown in collagen gels, the MDCK(LT) cells form branching tubules, and their 
      conditioned media produce the scattering of monolayer cultured MDCK cells. These 
      last properties are reminiscent of those induced by hepatocyte growth 
      factor/scatter factor (HGF/SF). Moreover, the HGF/SF protein was detected by 
      Western blotting in the MDCK(LT)-conditioned medium. The production of HGF/SF is 
      specifically induced by LT-RB inactivation, because Ras transformation of MDCK 
      cells fails to induce the production of this factor. These results demonstrate 
      that inactivation of RB family proteins in these cells is at the origin of a 
      HGF/SF autocrine loop.
FAU - Martel, C
AU  - Martel C
AD  - Universite Rene Descartes, Paris, France.
FAU - Harper, F
AU  - Harper F
FAU - Cereghini, S
AU  - Cereghini S
FAU - Noe, V
AU  - Noe V
FAU - Mareel, M
AU  - Mareel M
FAU - Cremisi, C
AU  - Cremisi C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Growth Differ
JT  - Cell growth & differentiation : the molecular biology journal of the American 
      Association for Cancer Research
JID - 9100024
RN  - 0 (Antigens, Polyomavirus Transforming)
RN  - 0 (Biomarkers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hnf1b protein, rat)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Transcription Factors)
RN  - 138674-15-4 (Hepatocyte Nuclear Factor 1-beta)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Antigens, Polyomavirus Transforming/biosynthesis/*pharmacology
MH  - Biomarkers
MH  - Cell Differentiation/genetics
MH  - Cell Line
MH  - DNA-Binding Proteins/metabolism
MH  - Dogs
MH  - Epithelial Cells
MH  - Epithelium/metabolism/pathology
MH  - Fibroblasts/cytology/metabolism/pathology
MH  - Gene Transfer Techniques
MH  - Genes, myc
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Hepatocyte Nuclear Factor 1-beta
MH  - Intercellular Junctions/genetics/ultrastructure
MH  - Microvilli/genetics/ultrastructure
MH  - Neoplasm Invasiveness/pathology/ultrastructure
MH  - Nuclear Proteins/metabolism
MH  - Retinoblastoma Protein/genetics/*metabolism
MH  - Transcription Factors/metabolism
EDAT- 1997/02/01 00:00
MHDA- 1997/02/01 00:01
CRDT- 1997/02/01 00:00
PHST- 1997/02/01 00:00 [pubmed]
PHST- 1997/02/01 00:01 [medline]
PHST- 1997/02/01 00:00 [entrez]
PST - ppublish
SO  - Cell Growth Differ. 1997 Feb;8(2):165-78.