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return kwic search for specific out of >500 occurrences
279736 occurrences (No.90 in the rank) during 5 years in the PubMed. [no cache] 500 found

236) Using broad-spectrum and specific MMP inhibitors, we establish that MMP-1, but not MMP-2 and -9, plays a key role in 5-azadC-enhanced cell invasion.

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PMID:24038389 DOI:10.1002/mc.22071

2015 Molecular carcinogenesis

* The DNA hypomethylating agent, 5-aza-2'-deoxycytidine, enhances tumor cell invasion through a transcription-dependent modulation of MMP-1 expression in human fibrosarcoma cells.

- In diseases such as cancer, cells need to degrade the extracellular matrix (ECM) and therefore require high protease levels. Thus, aberrant tissue degradation is associated to matrix metalloproteinases (MMPs) overexpression resulting from different mechanisms including epigenetic events. One of the most characterized epigenetic mechanisms is DNA methylation causing changes in chromatin conformation, thereby decreasing the accessibility to the transcriptional machinery and resulting in a robust gene silencing. Modulation of DNA methylation by DNA hypomethylating agents such as 5-aza-2'-deoxycytidine (5-azadC) is widely used in epigenetic anticancer treatments. Here, we focus on the effects of this drug on the expression level of MMP-1, -2, and -9 in human HT1080 fibrosarcoma cells. We demonstrate that 5-azadC increases MMP expression at both mRNA and protein levels, and promotes invasion potential of HT1080 cells. Using broad-spectrum and specific MMP inhibitors, we establish that MMP-1, but not MMP-2 and -9, plays a key role in 5-azadC-enhanced cell invasion. We show that 5-azadC induces MMP-1 expression through a transcriptional mechanism without affecting MMP-1 promoter methylation status. Finally, we demonstrate that 5-azadC treatment increases the nuclear levels of Sp1 and Sp3 transcription factors, and modulates their recruitment to the MMP-1 promoter, resulting in chromatin remodeling associated to 5-azadC-induced MMP-1 expression. All together, our data indicate that the hypomethylating agent 5-azadC modulates, mainly via Sp1 recruitment, MMP-1 expression resulting in an increased invasive potential of HT1080 cells.

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(1)15 to	(19)4 types	(37)2 attention	(55)2 lineages
(2)9 sequence	(20)3 characteristics	(38)2 barriers	(56)2 measures
(3)7 and	(21)3 features	(39)2 computational	(57)2 miRNAs
(4)7 cell	(22)3 job	(40)2 constitutive	(58)2 molecular
(5)7 variations	(23)3 target	(41)2 criteria	(59)2 neuronal
(6)6 cognitive	(24)3 tendon	(42)2 deficits	(60)2 or
(7)6 genes	(25)3 therapy	(43)2 differences	(61)2 parameters
(8)6 surface	(26)3 type	(44)2 divergence	(62)2 phytotoxicity
(9)5 antibodies	(27)3 variation	(45)2 effect	(63)2 polymerase
(10)5 for	(28)2 null	(46)2 elements	(64)2 primers
(11)5 phobias	(29)2 ECM	(47)2 ethnocultural	(65)2 protein
(12)4 brain	(30)2 IgG	(48)2 extracellular	(66)2 proteins
(13)4 effects	(31)2 PCR	(49)2 fault	(67)2 recommendations
(14)4 growth	(32)2 age-dependent	(50)2 function	(68)2 requirements
(15)4 incidence	(33)2 analysis	(51)2 genetic	(69)2 self-efficacy
(16)4 manner	(34)2 antigen	(52)2 genomic	(70)2 targeted
(17)4 motor	(35)2 antigens	(53)2 information	(71)2 tests
(18)4 needs	(36)2 approach	(54)2 inhibitors

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--- WordNet output for specific --- =>特有の, 特効薬, 明確な, 特定の, 種の, はっきりした Overview of noun specific The noun specific has 2 senses (no senses from tagged texts) 1. particular, specific -- (a fact about some part (as opposed to general); "he always reasons from the particular to the general") 2. specific -- (a medicine that has a mitigating effect on a specific disease; "quinine is a specific for malaria") Overview of adj specific The adj specific has 4 senses (first 2 from tagged texts) 1. (39) specific -- ((sometimes followed by `to') applying to or characterized by or distinguishing something particular or special or unique; "rules with specific application"; "demands specific to the job"; "a specific and detailed account of the accident") 2. (5) specific -- (stated explicitly or in detail; "needed a specific amount") 3. specific -- (relating to or distinguishing or constituting a taxonomic species; "specific characters") 4. specific -- (being or affecting a disease produced by a particular microorganism or condition; used also of stains or dyes used in making microscope slides; "quinine is highly specific for malaria"; "a specific remedy"; "a specific stain is one having a specific affinity for particular structural elements") --- WordNet end ---