Protease nexin-1 expression is altered in human breast cancer.
Protease nexin-1 expression is altered in human breast cancer.
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DOI：
10.1186/1475-2867-6-16
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发表时间：
2006-05-31
影响因子：
5.8
通讯作者：
Orlando RA
中科院分区：
文献类型：
--
作者：
Candia BJ;Hines WC;Heaphy CM;Griffith JK;Orlando RA
尿激酶型纤溶酶原激活剂(UPA)是一种丝氨酸蛋白酶，通过介导细胞外基质蛋白的降解，促进细胞运动，在乳腺癌转移过程中发挥关键作用。在更晚期的乳腺癌中，uPA活性显著上调，并作为患者预后不良的指标。传统上，uPA活性的调节，特别是在乳腺癌中，被认为是由1型纤溶酶原激活物抑制物(PAI-1)介导的。然而，我们最近发现，一种鲜为人知的uPA天然抑制物，即蛋白酶Nexin 1(PN-1)，在正常人类乳腺组织中表达。基于这一观察，我们调查了PN-1是否也在人类乳腺癌中表达，在那里它可能有助于调节uPA并参与转移表型的发展。应用实时定量聚合酶链式反应技术，检测了26例人乳腺肿瘤组织中PN-1mRNA的表达，并与10例正常乳腺组织进行了比较。由于已知PAI-1和uPA在转移性乳腺癌中的表达水平升高，我们还测量了26个肿瘤样本中它们的水平，以便与PN-1的表达进行直接比较。我们发现，PN-1的表达比在正常乳腺组织中发现的要高；在接受检查的26个人的乳腺肿瘤中，有21个增加了1.5-3.5倍。正如预期的那样，在大多数乳腺肿瘤中，PAI-1和uPA的mRNA水平都显著升高；26个肿瘤中有19个表达PAI-1，26个肿瘤中有22个表达uPA。这些数据的分位数框图表明，乳腺肿瘤组织中PN-1表达的增加与PAI-1和uPA表达水平的增加直接相关。PN-1在乳腺癌中的表达升高，且其表达增强与PAI-1和uPA的表达升高直接相关，提示PN-1可能参与调节uPA介导的肿瘤细胞的运动和转移扩散。
Urokinase-type Plasminogen Activator (uPA), a serine protease, plays a pivotal role in human breast cancer metastasis by mediating the degradation of extracellular matrix proteins and promoting cell motility. In more advanced breast cancers, uPA activity is significantly up regulated and serves as a prognostic indicator of poor patient outcome. Classically, regulation of uPA activity, especially in breast cancers, is thought to be mediated by Type 1 Plasminogen Activator Inhibitor (PAI-1). However, we have recently found that a lesser known natural inhibitor of uPA, Protease Nexin 1 (PN-1), is expressed in normal human mammary tissue. Based on this observation, we investigated if PN-1 is also expressed in human breast cancers where it may contribute to the regulation of uPA and participate in the development of a metastatic phenotype. Using quantitative real-time PCR analysis, we measured PN-1 mRNA expression in tissues obtained from 26 human breast tumor biopsies and compared these values with those obtained from 10 normal breast tissue samples. Since both PAI-1 and uPA expression levels are known to be elevated in metastatic breast cancer, we also measured their levels in our 26 tumor samples for direct comparison with PN-1 expression. We found that PN-1 expression was elevated over that found in normal mammary tissue; an increase of 1.5- to 3.5-fold in 21 of 26 human breast tumors examined. As anticipated, both PAI-1 and uPA mRNA levels were significantly higher in the majority of breast tumors; 19 of 26 tumors for PAI-1 and 22 of 26 tumors for uPA. A quantile box plot of these data demonstrates that the elevated PN-1 expression in breast tumor tissues directly correlates with the increased expression levels found for PAI-1 and uPA. The fact that PN-1 expression is elevated in human breast cancer, and that its increased expression is directly correlated with increases measured for PAI-1 and uPA, suggests that PN-1 may contribute to the regulation of uPA-mediate tumor cell motility and metastatic spread.
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影响因子：
5.6
作者：
KNAUER, DJ;THOMPSON, JA;CUNNINGHAM, DD
通讯作者：
CUNNINGHAM, DD
影响因子：
2.9
作者：
LINDNER, J;ZINSER, G;SCHACHNER, M
通讯作者：
SCHACHNER, M
影响因子：
8.8
作者：
Knoop, A;Andreasen, P A;Andersen, J A;Hansen, S;Laenkholm, A V;Simonsen, A C;Andersen, J;Overgaard, J;Rose, C
通讯作者：
Rose, C
影响因子：
64.5
作者：
BAKER, JB;LOW, DA;CUNNINGHAM, DD
通讯作者：
CUNNINGHAM, DD
影响因子：
2
作者：
Look, MP
通讯作者：
Look, MP