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首页> 外文期刊>Breast cancer research and treatment. >Urokinase plasminogen activator system gene expression is increased in human breast carcinoma and its bone metastases--a comparison of normal breast tissue, non-invasive and invasive carcinoma and osseous metastases.
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Urokinase plasminogen activator system gene expression is increased in human breast carcinoma and its bone metastases--a comparison of normal breast tissue, non-invasive and invasive carcinoma and osseous metastases.

机译：尿激酶纤溶酶原激活物系统基因在人乳腺癌及其骨转移中的表达增加-与正常乳腺组织，非浸润性和浸润性癌以及骨转移的比较。

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The urokinase plasminogen activator (uPA) system has been widely associated with the development of breast carcinoma. However, the role of the urokinase pathway in the development of osseous breast cancer metastases has been largely overlooked. We studied the expression of uPA, urokinase plasminogen activator receptor (uPAR)- and plasminogen activator inhibitor type-1 (PAI-1) in human breast carcinomas and their bone metastases, using in situ hybridisation. Studies were performed using paraffin-embedded tissue from 13 ductal carcinomas, 23 invasive ductal carcinomas, five normal breasts and 25 bone metastases. The majority of the tumours examined expressed low to moderate levels of uPA mRNA and low to high levels of uPAR and PAI-1 mRNA, which was predominantly localised to the epithelial tumour cells. There was slight over-expression of uPA and PAI-1 mRNA and a marked increase in uPAR mRNA expression in the malignant tumours compared with benign tissue. Overall, uPAR and PAI-1 mRNA expression was found to be more variable than uPA mRNA, suggesting a possible role of the receptor and inhibitor in the regulation of uPA activity. Increased alpha1(I) procollagen (COL) and osteopontin (OPN) mRNA expression was detected, primarily in the stromal cells, in malignant tumours compared with the benign tissue. The increased expression of the components of the uPA system on the epithelial tumour cells may account for the activation of the proteolytic cascade that occurs during breast cancer metastasis to bone. Furthermore, the over-expression of COL and OPN suggests a possible interaction between these matrix proteins and the uPA system.
机译：尿激酶纤溶酶原激活剂（uPA）系统已与乳腺癌的发展广泛相关。然而，尿激酶途径在骨性乳腺癌转移发展中的作用已被大大忽略。我们使用原位杂交研究了uPA，尿激酶纤溶酶原激活物受体（uPAR）-和纤溶酶原激活物抑制剂1型（PAI-1）在人乳腺癌及其骨转移中的表达。使用来自13个导管癌，23个浸润性导管癌，5个正常乳房和25个骨转移的石蜡包埋组织进行了研究。检查的大多数肿瘤表达低至中等水平的uPA mRNA和低至高水平的uPAR和PAI-1 mRNA，这些肿瘤主要定位于上皮肿瘤细胞。与良性组织相比，恶性肿瘤中uPA和PAI-1 mRNA略有过度表达，uPAR mRNA表达显着增加。总体而言，发现uPAR和PAI-1 mRNA表达比uPA mRNA更具可变性，表明受体和抑制剂可能在uPA活性调节中发挥作用。与良性组织相比，在恶性肿瘤中主要在基质细胞中检测到了alpha1（I）前胶原（COL）和骨桥蛋白（OPN）mRNA表达的增加。 uPA系统的成分在上皮肿瘤细胞上表达的增加可能解释了在乳腺癌转移至骨的过程中发生的蛋白水解级联反应的激活。此外，COL和OPN的过度表达表明这些基质蛋白与uPA系统之间可能存在相互作用。

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