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

• 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
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.20520

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.