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

✍ Scribed by Carmilia Jiménez Ramírez; Juliet M. Haberbusch; Dianne Robert Soprano; Kenneth J. Soprano

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 278 KB
• Volume: 96
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20520

✦ Synopsis

Abstract

In previous studies we have shown that all‐trans retinoic acid (__at__RA)‐treatment of the __at__RA‐sensitive ovarian carcinoma cell line CA‐OV3 repressed AP‐1 activity by about 50%, while a similar effect was not observed in the __at__RA‐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 __at__RA inhibits the growth of __at__RA‐sensitive CA‐OV3 cells. In the present studies, we investigated further the molecular mechanism by which AP‐1 activity is repressed by __at__RA. 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 __at__RA. However, the activity of the protein phosphatase PP2A was found to increase 24 h following __at__RA treatment in CA‐OV3 cells. Moreover, the catalytic subunit of PP2A was found to associate with c‐Jun in vivo following __at__RA treatment. Since the inhibition of AP‐1 activity following __at__RA 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 __at__RA‐induced repression of AP‐1. © 2005 Wiley‐Liss, Inc.