Tumor necrosis factor-alpha, a new tumor promoter, engendered by biochemical studies of okadaic acid.

Abstract

Okadaic acid is a potent tumor promoter on mouse skin and in rat glandular stomach, and an inhibitor of PP-1 and PP-2A. How okadaic acid biochemically induces tumor promotion in these tissues was reviewed. Okadaic acid bound to a catalytic subunit of PP-1 and PP-2A and induced hyperphosphorylation of proteins, such as vimentin, cytokeratins, HSP 27, and tumor suppressor gene products. Since one of the okadaic acid class compounds, microcystin-LR, induced tumor promotion in rat liver, the okadaic acid pathway mediated through inhibition of PP-1 and PP-2A is seen to be a general biochemical process of tumor promotion in various organs. The biochemical mimicry of okadaic acid by TNF-alpha led us to find that TNF-alpha is an endogenous tumor promoter. The study of tumor promotion in two-stage carcinogenesis experiments with the okadaic acid class of compounds engendered a new tumor promoter applicable to human cancer development.

• Authors: H Fujiki, M Suganuma
• Journal: Journal of biochemistry (J Biochem) Vol. 115 Issue 1 Pg. 1-5 (Jan 1994) ISSN: 0021-924X [Print] England
• PMID: 8188614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Carcinogens
• Ethers, Cyclic
• Receptors, Drug
• Tumor Necrosis Factor-alpha
• okadaic acid receptor
• Okadaic Acid
• Phosphoprotein Phosphatases

Topics

• Animals
• Carcinogens (pharmacology)
• Cell Transformation, Neoplastic (genetics, metabolism)
• Ethers, Cyclic (pharmacology)
• Gene Expression Regulation (drug effects)
• Humans
• Okadaic Acid
• Phosphoprotein Phosphatases (antagonists & inhibitors)
• Phosphorylation (drug effects)
• Receptors, Drug (physiology)
• Transcription, Genetic (drug effects)
• Tumor Necrosis Factor-alpha (physiology)