Retinoic acid induced repression of AP-1 activity is mediated by protein phosphatase 2A in ovarian carcinoma cells

In previous studies we have shown that all‐trans retinoic acid (atRA)‐treatment of the atRA‐sensitive ovarian carcinoma cell line CA‐OV3 repressed AP‐1 activity by about 50%, while a similar effect was not observed in the atRA‐resistant ovarian carcinoma cell line, SK‐OV3. These results suggested th...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular biochemistry 2005-09, Vol.96 (1), p.170-182
Main Authors: Ramírez, Carmilia Jiménez, Haberbusch, Juliet M., Soprano, Dianne Robert, Soprano, Kenneth J.
Format: Article
Language:English
Subjects:
AP-1
Carcinoma - enzymology
Cell Line, Tumor
Dimerization
Down-Regulation - physiology
Female
Humans
JNK Mitogen-Activated Protein Kinases - metabolism
Ovarian Neoplasms - enzymology
Phosphoprotein Phosphatases - physiology
Phosphorylation
PP2A
retinoic acid
Serine - metabolism
Transcription Factor AP-1 - antagonists & inhibitors
Tretinoin - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In previous studies we have shown that all‐trans retinoic acid (atRA)‐treatment of the atRA‐sensitive ovarian carcinoma cell line CA‐OV3 repressed AP‐1 activity by about 50%, while a similar effect was not observed in the atRA‐resistant ovarian carcinoma cell line, SK‐OV3. These results suggested that the repression of AP‐1 activity may be one of the mechanisms by which atRA inhibits the growth of atRA‐sensitive CA‐OV3 cells. In the present studies, we investigated further the molecular mechanism by which AP‐1 activity is repressed by atRA. We show that the repression of AP‐1 activity correlates with an increase in JunB protein expression and a decrease in N‐terminal phosphorylation of c‐Jun. The decrease in N‐terminal phosphorylation of c‐Jun does not appear to be modulated by JNK or ERK, since their protein expression patterns and kinase activity do not correlate with the repression of AP‐1 activity following treatment with atRA. However, the activity of the protein phosphatase PP2A was found to increase 24 h following atRA treatment in CA‐OV3 cells. Moreover, the catalytic subunit of PP2A was found to associate with c‐Jun in vivo following atRA treatment. Since the inhibition of AP‐1 activity following atRA treatment of CA‐OV3 cells was abolished in the presence of specific PP2A inhibitors, it is likely that PP2A plays an important role in the atRA‐induced repression of AP‐1. © 2005 Wiley‐Liss, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.20520