Specific genes involved in synthesis and editing of heparan sulfate proteoglycans show altered expression patterns in breast cancer.
Specific genes involved in synthesis and editing of heparan sulfate proteoglycans show altered expression patterns in breast cancer.
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DOI：
10.1186/1471-2407-13-24
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发表时间：
2013-01-17
期刊：
影响因子：
3.8
通讯作者：
Quirós LM
中科院分区：
文献类型：
--
作者：
Fernández-Vega I;García O;Crespo A;Castañón S;Menéndez P;Astudillo A;Quirós LM
一组特定基因的表达控制硫酸乙酰肝素蛋白聚糖（HSPG）的不同结构，其参与癌细胞的生长、侵袭和转移特性。本研究的目的是增加乳腺癌中HSPG改变的知识。23例浸润性导管腺癌（IDC），转移性和非转移性进行了研究。使用硫酸乙酰肝素（HS）链结构的转录组学方法，采用qPCR分析参与其生物合成和编辑的酶以及蛋白聚糖核心蛋白的表达。由于这些蛋白聚糖中的一些也可以携带硫酸软骨素链，我们将研究扩展到包括参与这些糖胺聚糖生物合成的基因。组织化学技术也被用来分析特定基因的组织表达，显示出显着的表达差异，潜在的利益。在大约70%的分析基因中没有检测到转录的显著变化。然而，13个基因在两种肿瘤类型中都表现出变化（40%在转移性肿瘤中表现出更强烈的失调），而5个基因仅在非转移性肿瘤中表现出变化。变化与3个核心蛋白有关：syndecan-1的过度表达和磷脂酰肌醇蛋白聚糖-3和串珠素的低表达。HS合成的影响，一些3-O-磺基转移酶的成绩单，NDST 4的表达水平较低，只有在非转移性肿瘤，细胞外硫酸酯酶的水平较高。此外，硫酸软骨素的表达也受到相当大的影响，涉及糖链的合成和所有位置的硫酸化。然而，促转移酶乙酰肝素酶没有表现出mRNA表达的显着变化，尽管在转移性肿瘤中，它似乎与最稳定形式的mRNA水平增加有关。最后，乙酰肝素酶2的表达，显示抗转移的功能，经历了强烈的失调，在所有分析的患者。IDC显示HSPG基因表达的改变;主要是蛋白聚糖的表达和定位以及糖胺聚糖链的硫酸化模式，这取决于肿瘤的转移性质。此外，抗增殖分子乙酰肝素酶2经历了强烈的去调节，从而突出了它作为一个潜在的有趣的诊断因子。
The expression of a specific set of genes controls the different structures of heparan sulfate proteoglycans (HSPGs), which are involved in the growth, invasion and metastatic properties of cancerous cells. The purpose of this study is to increase knowledge of HSPG alterations in breast cancer. Twenty-three infiltrating ductal adenocarcinomas (IDCs), both metastatic and non-metastatic were studied. A transcriptomic approach to the structure of heparan sulfate (HS) chains was used, employing qPCR to analyze both the expression of the enzymes involved in their biosynthesis and editing, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate chains, we extended the study to include the genes involved in the biosynthesis of these glycosaminoglycans. Histochemical techniques were also used to analyze tissular expression of particular genes showing significant expression differences, of potential interest. No significant change in transcription was detected in approximately 70% of analyzed genes. However, 13 demonstrated changes in both tumor types (40% showing more intense deregulation in the metastatic), while 5 genes showed changes only in non-metastatic tumors. Changes were related to 3 core proteins: overexpression of syndecan-1 and underexpression of glypican-3 and perlecan. HS synthesis was affected by lower levels of some 3-O-sulfotransferase transcripts, the expression of NDST4 and, only in non metastatic tumors, higher levels of extracellular sulfatases. Furthermore, the expression of chondroitin sulfate also was considerably affected, involving both the synthesis of the saccharidic chains and sulfations at all locations. However, the pro-metastatic enzyme heparanase did not exhibit significant changes in mRNA expression, although in metastatic tumors it appeared related to increased levels of the most stable form of mRNA. Finally, the expression of heparanase 2, which displays anti-metastatic features, experienced a strong deregulation in all patients analyzed. IDCs show alterations in the expression of HSPG genes; principally the expression and localization of proteoglycans and the sulfation patterns of glycosaminoglycan chains, depending on the metastatic nature of the tumor. In addition, the anti-proliferative molecule heparanase 2 experiences strong deregulation, thus highlighting it as a potentially interesting diagnostic factor.
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影响因子：
4.8
作者：
Arvatz, Gil;Barash, Uri;Vlodavsky, Israel
通讯作者：
Vlodavsky, Israel
影响因子：
4.8
作者：
Mikami, T;Mizumoto, S;Sugahara, K
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Sugahara, K
影响因子：
15.9
作者：
Esko, JD;Lindahl, U
通讯作者：
Lindahl, U
影响因子：
4.8
作者：
Levy-Adam, Flonia;Feld, Sari;Vlodavsky, Israel
通讯作者：
Vlodavsky, Israel
影响因子：
4.8
作者：
Aikawa, J;Grobe, K;Esko, JD
通讯作者：
Esko, JD