SEL1L affects human pancreatic cancer cell cycle and invasiveness through modulation of PTEN and genes related to cell-matrix interactions
SEL1L affects human pancreatic cancer cell cycle and invasiveness through modulation of PTEN and genes related to cell-matrix interactions
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DOI：
10.1593/neo.05451
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发表时间：
2005-11-01
期刊：
影响因子：
4.8
通讯作者：
Biunno, I
中科院分区：
文献类型：
--
作者：
Cattaneo, M;Fontanella, E;Biunno, I
此前，据报道，SEL 1 L能够在体外和体内降低人胰腺肿瘤细胞的侵袭行为。为了深入了解SEUL在肿瘤侵袭中的作用，我们对胰腺癌细胞系Suit-2进行了两种互补策略的基因表达分析：通过在诱导型启动子下稳定转染整个cDNA和通过RNA介导的干扰上调和下调SEL 1 L表达。SuperArray和实时荧光分析显示SEUL调节基质金属蛋白酶抑制剂TIMP 1（P < .04-.03）和TIMP 2（P < .03-.05）以及PTEN基因（P < .03-.05）的表达。基因表达调节与侵袭能力的降低（P <0.05）和G1期SEL 1 L表达细胞的积累相关。两者合计，我们的数据表明，SEOL改变参与细胞外基质重塑的介质的表达，通过创建一个微环境，这是不利的侵入性生长，并通过影响细胞周期的进展，通过促进G1积累。
Previously, it was reported that SEL1L is able to decrease the aggressive behavior of human pancreatic tumor cells both in vitro and in vivo. To gain insights into the involvement of SEUL in tumor invasion, we performed gene expression analysis on the pancreatic cancer cell line Suit-2 subjected to two complementary strategies: upregulation and downregulation of SEL1L expression by stable transfection of the entire cDNA under an inducible promoter and by RNA-mediated interference. SuperArray and real-time analysis revealed that SEUL modulates the expression of the matrix metalloproteinase inhibitors TIMP1 (P < .04-.03) and TIMP2 (P < .03-.05), and the PTENgene (P < .03-.05). Gene expression modulations correlate with the decrease in invasive ability (P < .05) and in accumulation of SEL1L-expressing cells in G1. Taken together, our data indicate that SEOL alters the expression of mediators involved in the remodeling of the extracellular matrix by creating a microenvironment that is unfavorable to invasive growth and by affecting cell cycle progression through promotion of G1 accumulation.