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338) Maximal induction of both cyclooxygenase-2 and inducible nitric oxide synthase in epidermis following treatment with CHRY was also dependent on the presence of functional Stat1.
* A novel mechanism of skin tumor promotion involving interferon-gamma (IFNγ)/signal transducer and activator of transcription-1 (Stat1) signaling.
- The current study was designed to explore the role of signal transducer and activator of transcription 1 (Stat1) during tumor promotion using the mouse skin multistage carcinogenesis model. Topical treatment with both 12-O-tetradecanoylphorbol-13-acetate (TPA) and 3-methyl-1,8-dihydroxy-9-anthrone (chrysarobin or CHRY) led to rapid phosphorylation of Stat1 on both tyrosine (Y701) and serine (S727) residues in epidermis. CHRY treatment also led to upregulation of unphosphorylated Stat1 (uStat1) at later time points. CHRY treatment also led to upregulation of interferon regulatory factor 1 (IRF-1) mRNA and protein, which was dependent on Stat1. Further analyses demonstrated that topical treatment with CHRY but not TPA upregulated interferon-gamma (IFNγ) mRNA in the epidermis and that the induction of both IRF-1 and uStat1 was dependent on IFNγ signaling. Stat1 deficient (Stat1(-/-) ) mice were highly resistant to skin tumor promotion by CHRY. In contrast, the tumor response (in terms of both papillomas and squamous cell carcinomas) was similar in Stat1(-/-) mice and wild-type littermates with TPA as the promoter. Maximal induction of both cyclooxygenase-2 and inducible nitric oxide synthase in epidermis following treatment with CHRY was also dependent on the presence of functional Stat1. These studies define a novel mechanism associated with skin tumor promotion by the anthrone class of tumor promoters involving upregulation of IFNγ signaling in the epidermis and downstream signaling through activated (phosphorylated) Stat1, IRF-1 and uStat1.
=>機能の, 関数の, 機能する, 機能上の, 実用的な, 機能的な
Overview of adj functional
The adj functional has 6 senses (first 2 from tagged texts)
1. (3) functional -- (designed for or capable of a particular function or use; "a style of writing
in which every word is functional"; "functional architecture")
2. (1) functional -- (involving or affecting function rather than physiology; "functional deafness")
3. functional -- (relating to or based on function especially as opposed to structure; "the problem
now is not a constitutional one; it is a functional one"; "delegates elected on a functional rather
than a geographical basis")
4. functional, usable, useable, operable, operational -- (fit or ready for use or service; "the
toaster was still functional even after being dropped"; "the lawnmower is a bit rusty but still
usable"; "an operational aircraft"; "the dishwasher is now in working order")
5. functional -- (designed for or adapted to a function or use; "functional education selects
knowledge that is concrete and usable rather than abstract and theoretical"; "functional
architecture")
6. running, operative, functional, working -- ((of e.g. a machine) performing or capable of
performing; "in running (or working) order"; "a functional set of brakes")
--- WordNet end ---