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【Nature】SATB1重新编程基因表达促进乳腺肿瘤生长
Mechanisms underlying global changes in gene expression during tumour progression are poorly understood. SATB1 is a genome organizer that tethers multiple genomic loci and recruits chromatin-remodelling enzymes to regulate chromatin structure and gene expression. Here we show that SATB1 is expressed by aggressive breast cancer cells and its expression level has high prognostic significance (P < 0.0001), independent of lymph-node status. RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells altered the expression of >1,000 genes, reversing tumorigenesis by restoring breast-like acinar polarity and inhibiting tumour growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non-aggressive (SKBR3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo. SATB1 delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumour-suppressor genes. SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression.
http://www.nature.com/nature/journal/v452/n7184/abs/nature06781.html 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis
STAB1重编码基因表达可促进乳腺肿瘤生长和转移
Mechanisms underlying global changes in gene expression during tumour progression are poorly understood.
关于肿瘤进展中基因表达的总体改变的机制还不清楚。
SATB1 is a genome organizer that tethers multiple genomic loci and recruits chromatin-remodelling enzymes to regulate chromatin structure and gene expression.
STAB1是一种基因组组成子，其作用是通过联结多个基因组位点和结合染色质重构酶来调控染色质结构和基因表达。Here we show that SATB1 is expressed by aggressive breast cancer cells and its expression level has high prognostic significance (P < 0.0001), independent of lymph-node status. 研究者们研究发现STAB1表达于侵袭性乳腺癌细胞中，而且研究结果还显示无论有无淋巴结转移，其表达水平与预后有关。
RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells altered the expression of >1,000 genes, reversing tumorigenesis by restoring breast-like acinar polarity and inhibiting tumour growth and metastasis in vivo.
体内实验发现应用RNA干扰介导技术敲除高度侵袭性乳腺癌细胞系（MDA-MB-231）中STAB1基因后，该细胞系中>1000个基因表达发生改变，乳腺样腺泡极性恢复和肿瘤生长和转移被抑制，从而逆转了肿瘤发生。
Conversely, ectopic SATB1 expression in non-aggressive (SKBR3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo.
相反，在非侵袭性细胞系（SKBR3）中异常的STAB1表达可导致侵袭性肿瘤表型的基因表达，体内实验显示获得了转移活性。
SATB1 delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumour-suppressor genes.
STAB1在靶基因位点的特异性表观遗传学改变，直接上调了转移相关基因而下调了肿瘤抑制基因。
SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression.
乳腺肿瘤中STAB1重编码染色质构型和转录谱促进了肿瘤生长和转移。这是一个肿瘤进展的新的机制。 STAB1重编码基因表达可促进乳腺肿瘤生长和转移
关于肿瘤进展中基因表达的总体改变的机制还不清楚。STAB1是一种基因组组成子，其作用是通过联结多个基因组位点和结合染色质重构酶来调控染色质结构和基因表达。研究者们研究发现STAB1表达于侵袭性乳腺癌细胞中，而且研究结果还显示无论有无淋巴结转移，其表达水平与预后有关。体内实验发现应用RNA干扰介导技术敲除高度侵袭性乳腺癌细胞系（MDA-MB-231）中STAB1基因后，该细胞系中>1000个基因表达发生改变，乳腺样腺泡极性恢复和肿瘤生长和转移被抑制，从而逆转了肿瘤发生。相反，在非侵袭性细胞系（SKBR3）中异常的STAB1表达可导致侵袭性肿瘤表型的基因表达，体内实验显示获得了转移活性。STAB1在靶基因位点的特异性表观遗传学改变，直接上调了转移相关基因而下调了肿瘤抑制基因。乳腺肿瘤中STAB1重编码染色质构型和转录谱促进了肿瘤生长和转移。这是一个肿瘤进展的新的机制。
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作者:admin@医学,生命科学 2010-12-25 17:11
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