PMID- 9181055
OWN - NLM
STAT- MEDLINE
DCOM- 19970820
LR  - 20161018
IS  - 0100-879X (Print)
IS  - 0100-879X (Linking)
VI  - 29
IP  - 9
DP  - 1996 Sep
TI  - Ha-ras oncogene transformation abolishes retinoic acid-induced reduction of 
      intracellular fibronectin.
PG  - 1127-31
AB  - All-trans-retinoic acid (RA) is a master regulator of cell differentiation and in 
      this process it greatly influences cell adhesion and the elaboration of the 
      extracellular matrix. Therefore, we were interested in the effect of RA on the 
      biosynthesis of fibronectin (FN). RA reduced the level of intracellular FN in a 
      time- and concentration-dependent fashion in NIH-3T3 cells, but not in NIH-3T3 
      cells transformed by an activated Ha-ras oncogene. Since the steady-state level 
      of FN transcripts did not change after treatment of the cells with RA for various 
      times or concentrations, RA probably acts at the translational level. In NIH-3T3 
      cells, RA had distinct effects on different receptors, from decreasing retinoic 
      acid receptor (RAR)alpha to increasing RAR beta expression to no effect on RAR 
      gamma. Transformation of NIH-3T3 cells with an activated Ha-ras oncogene 
      downmodulated RAR expression and also abolished responsiveness to RA. A variety 
      of approaches permitted the following conclusions: 1) RA-dependent FN 
      downmodulation is mediated by RARs, 2) retinoid X receptors (RXRs) mediate the 
      observed reduction of RAR alpha by RA, and 3) the blockade of RA responsiveness 
      by Ha-ras-transfected cells cannot be overcome by overexpression of RAR alpha. 
      These studies have identified fibronectin and RAR alpha as RA targets in 
      fibroblast cells and have shown that oncogenic transformation renders the cells 
      resistant to RA action.
FAU - De-Luca, L M
AU  - De-Luca LM
AD  - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer 
      Institute, NIH, Bethesda, Maryland 20892, USA.
FAU - Scita, G
AU  - Scita G
LA  - eng
PT  - Journal Article
PL  - Brazil
TA  - Braz J Med Biol Res
JT  - Brazilian journal of medical and biological research = Revista brasileira de 
      pesquisas medicas e biologicas
JID - 8112917
RN  - 0 (Fibronectins)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Fibronectins/*physiology
MH  - Gene Expression Regulation
MH  - Genes, ras/*physiology
MH  - Humans
MH  - Intracellular Membranes
MH  - Proto-Oncogene Proteins p21(ras)/*physiology
MH  - Tretinoin/*physiology
EDAT- 1996/09/01 00:00
MHDA- 1996/09/01 00:01
CRDT- 1996/09/01 00:00
PHST- 1996/09/01 00:00 [pubmed]
PHST- 1996/09/01 00:01 [medline]
PHST- 1996/09/01 00:00 [entrez]
PST - ppublish
SO  - Braz J Med Biol Res. 1996 Sep;29(9):1127-31.