Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter.

Suganuma, Masami; Fujiki, Hirota; Suguri, Hiroko; Yoshizawa, Shigeru; Hirota, Mitsuru; Nakayasu, Michie; Ojika, Makoto; Wakamatsu, Kazumasa; Yamada, Kiyoyuki; Sügimura, Takashi

doi:10.1073/pnas.85.6.1768

Cited by 561 publications

(260 citation statements)

References 18 publications

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“…Okadaic acid inhibits the serine-threonine phosphatases 1 (PP-1), 2A (PP-2A) (Bialojan and Takai, 1988) and 3 (PP-3) (Honkanen et al, 1991) by binding to their catalytic subunit and leads to the accumulation of hyperphosphorylated proteins (Haystead et al, 1989;Sassa et al, 1989). Okadaic acid is also a potent tumor promoter in mouse skin initiated with 7, 12 dimethylbenz [a]anthracene (DMBA) (Suganuma et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription

1999

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By performing in vitro kinase assays we found in papilloma producing 308 mouse keratinocytes that okadaic acid elevated activities of extracellular signalregulated kinase (ERK) 1/2, c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinases (MAPKs). This okadaic acid mediated activation of MAP kinases correlated with increased AP-1 binding to a consensus TPA responsive element (TRE) and elevated TRE dependent transcription. To determine the role of p38 MAP kinases in these processes we employed the speci®c p38 MAP kinase inhibitor SB 203580. Using orthophosphate labeling we showed a decrease in phosphorylation of MAPK activated protein kinase-2 (MAPKAP-K2) indicating reduced activity of p38 MAPKs utilizing this kinase as substrate. In contrast, we found that SB 203580 raised activities of ERK-1/2 and JNKs. Electrophoretic mobility shift assays revealed an increase in TRE binding activity in response to SB 203580 most likely resulting from increased expression of the major TRE binding components JunD and FosB as indicated by Western blot analyses. Increased TRE DNA binding failed to lead to increased transactivation correlating with the inability of SB 203580 to increase phosphorylation of these AP-1 proteins. These data indicate that SB 203580 sensitive p38 MAP kinases are not involved in okadaic acid mediated increases in TRE DNA binding and transactivation.

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Section: Introductionmentioning

confidence: 99%

Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription

1999

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“…The main toxins responsible for DSP are okadaic acid (OA), dinophysistoxins (DTX) 1 and 2 GagoMartínez et al, 1996a,b), and DTX3 (Figure 1), the latter being a complex mixture of 7-O-acyl esters of the first three formed as metabolites in shellfish . All of these cause gastrointestinal disorders, but the toxicological activity of greatest concern is the reported tumor promotion activities of OA and DTX1 (Suganuma et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Further Studies on the Analysis of DSP Toxin Profiles in Galician Mussels

Leão

Gago-Martı́nez

Vázquez

et al. 1999

J. Agric. Food Chem.

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“…Based on the observations that okadaic acid is both a strong inhibitor of the serine/threonine-speci®c protein phosphatase 2A (PP2A) (Bialojan and Takai, 1988) and a potent tumor promoter (Suganuma et al, 1988), it has been suggested that PP2A might be a tumor suppressor (Cohen and Cohen, 1989). Direct evidence for this suggestion has been lacking until recently, when Wang et al (1998) discovered that the gene encoding the b isoform of the A subunit of PP2A was altered in 15% of primary lung tumors (small-cell-and non-small-cell lung carcinomas), in 6% of lung tumorderived cell lines and in 15% of primary colon tumors.…”

Section: Introductionmentioning

confidence: 99%

Disruption of protein phosphatase 2A subunit interaction in human cancers with mutations in the Aα subunit gene

2001

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Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter.

Abstract: ABSTRACT

Cited by 561 publications

References 18 publications

Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription

Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription

Further Studies on the Analysis of DSP Toxin Profiles in Galician Mussels

Disruption of protein phosphatase 2A subunit interaction in human cancers with mutations in the Aα subunit gene

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