Localised breast cancer can be cured by surgery and adjuvant treatments, but mortality remains high as some tumours metastasize early. Perlecan is a basement membrane (BM) protein involved in tumour development and progression. Here, mRNA and protein expression of perlecan, and mRNA expression of matrix degrading enzymes were studied in normal breast and invasive breast cancer, and correlated to prognostic risk factors, in particular oestrogen status. Moreover, plasma levels of perlecan were measured in patients with breast cancer and compared with controls. mRNA data was extracted from the Cancer Genome Atlas database. Perlecan protein expression was visualized using immunofluorescence and plasma levels measured by ELISA assay. Perlecan mRNA levels were twice as high in normal breast compared with breast cancer tissue. A strong correlation was found between mRNA expression of perlecan and several matrix-degrading enzymes in oestrogen receptor positive (ER+) tumours. Perlecan protein was localized to both epithelial and vascular BMs, but absent in the stroma in normal breast. In breast cancer, the expression of perlecan in epithelial BM was fragmented or completely lost, with a marked upregulation of perlecan expression in the stroma. Significantly higher levels of perlecan were found in plasma of ER+ patients when compared with ER- patients. This study shows that perlecan expression and degradation in breast cancer may be linked to the ER status of the tumour.

中文翻译：

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Perlecan在乳腺癌中的表达和循环水平-对雌激素依赖性基质重构的影响。

局部乳腺癌可以通过手术和辅助治疗治愈，但是由于一些肿瘤早期转移，死亡率仍然很高。Perlecan是一种参与肿瘤发展和进展的基底膜（BM）蛋白。在这里，研究了正常乳腺癌和浸润性乳腺癌中perlecan的mRNA和蛋白表达以及基质降解酶的mRNA表达，它们与预后危险因素（尤其是雌激素状态）相关。此外，在乳腺癌患者中测量了血浆Perlecan的水平，并与对照组进行了比较。从癌症基因组图谱数据库中提取mRNA数据。使用免疫荧光观察Perlecan蛋白表达，并通过ELISA测定血浆水平。与乳腺癌组织相比，正常乳人的Perlecan mRNA水平高两倍。发现在雌激素受体阳性（ER +）肿瘤中，Perlecan的mRNA表达与几种基质降解酶之间存在很强的相关性。Perlecan蛋白定位于上皮和血管BMs，但在正常乳腺的基质中不存在。在乳腺癌中，上皮BM中perlecan的表达被破坏或完全丧失，基质中perlecan表达的明显上调。与ER-患者相比，ER +患者的血浆中Perlecan的含量明显更高。这项研究表明，乳癌中Perlecan的表达和降解可能与肿瘤的ER状态有关。但正常乳腺间质中不存在。在乳腺癌中，上皮BM中perlecan的表达被破坏或完全丧失，基质中perlecan表达的明显上调。与ER-患者相比，ER +患者的血浆中Perlecan的含量明显更高。这项研究表明，乳癌中Perlecan的表达和降解可能与肿瘤的ER状态有关。但正常乳腺间质中不存在。在乳腺癌中，上皮BM中perlecan的表达被破坏或完全丧失，基质中perlecan表达的明显上调。与ER-患者相比，ER +患者的血浆中Perlecan的含量明显更高。这项研究表明，乳癌中Perlecan的表达和降解可能与肿瘤的ER状态有关。