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731925 occurrences (No.6 in the rank) during 5 years in the PubMed. [no cache] 500 found

388) We show that 5-azadC induces MMP-1 expression through a transcriptional mechanism without affecting MMP-1 promoter methylation status.

--- ABSTRACT ---

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)183 of	(11)7 is	(21)3 indicating	(31)2 level,
(2)50 in	(12)6 analysis	(22)3 on	(32)2 pattern
(3)28 levels	(13)4 at	(23)3 via	(33)2 profiling
(4)25 and	(14)4 profile	(24)2 alkaline	(34)2 regulation
(5)23 was	(15)4 through	(25)2 between	(35)2 that
(6)21 null	(16)4 were	(26)2 but	(36)2 whereas
(7)11 level	(17)3 are	(27)2 cell	(37)2 which
(8)10 patterns	(18)3 changes	(28)2 during	(38)2 with
(9)8 profiles	(19)3 data	(29)2 from
(10)7 by	(20)3 for	(30)2 increased

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--- WordNet output for expression --- =>表現すること, 式, 表現, 表示, 言い回し, 表現法, 表情 Overview of noun expression The noun expression has 9 senses (first 6 from tagged texts) 1. (23) expression, look, aspect, facial expression, face -- (the feelings expressed on a person's face; "a sad expression"; "a look of triumph"; "an angry face") 2. (18) expression, manifestation, reflection, reflexion -- (expression without words; "tears are an expression of grief"; "the pulse is a reflection of the heart's condition") 3. (15) expression, verbal expression, verbalism -- (the communication (in speech or writing) of your beliefs or opinions; "expressions of good will"; "he helped me find verbal expression for my ideas"; "the idea was immediate but the verbalism took hours") 4. (5) saying, expression, locution -- (a word or phrase that particular people use in particular situations; "pardon the expression") 5. (4) formulation, expression -- (the style of expressing yourself; "he suggested a better formulation"; "his manner of expression showed how much he cared") 6. (4) formula, expression -- (a group of symbols that make a mathematical statement) 7. expression -- ((genetics) the process of expressing a gene) 8. construction, grammatical construction, expression -- (a group of words that form a constituent of a sentence and are considered as a single unit; "I concluded from his awkward constructions that he was a foreigner") 9. expression -- (the act of forcing something out by squeezing or pressing; "the expression of milk from her breast") --- WordNet end ---