Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer.
Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer.
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Desmoglein 2是胰腺癌中Kallikrein 7的底物。
DOI：
10.1186/1471-2407-8-373
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发表时间：
2008-12-17
期刊：
影响因子：
3.8
通讯作者：
Haun RS
中科院分区：
文献类型：
--
作者：
Ramani VC;Hennings L;Haun RS
在之前的一篇报道中，我们已经证明类糜蛋白酶样丝氨酸蛋白酶KLK7(KLK7/hK7)在胰腺癌中过表达。在正常皮肤中，hK7被认为通过促进桥粒成分(如桥粒蛋白)的降解而参与皮肤脱屑。因此，我们评估了hK7降解桥粒芯糖蛋白的能力，并检测了hK7表达对培养的胰腺癌细胞中桥粒芯糖蛋白2的影响。用免疫组织化学方法检测DSG1、Dsg2、Dsg3在胰腺癌细胞系BxPC-3和PANC-1中的表达，并用免疫印迹法检测它们在胰腺癌细胞系BxPC-3和PANC-1中的表达。通过体外降解实验考察了hK7对DSG1和Dsg2的降解能力。用稳定表达hK7的BxPC-3细胞检测hK7对细胞表面驻留Dsg2的影响。胰腺癌组织中DSG1和DSG2的表达水平均低于正常胰腺组织和慢性胰腺炎组织。在所检测的桥粒蛋白中，Dsg2在BxPC-3细胞表面有很强的表达。当hK7在该细胞系中过表达时，释放到培养上清液中的可溶性Dsg2的量与载体转染的对照细胞相比显著增加。胰腺肿瘤中细胞黏附成分DSG1和DSG2的数量减少，提示这些桥粒蛋白的缺失可能在胰腺癌的侵袭中起作用。体外降解实验表明，DSG1和DSG2都能被在胰腺癌中高表达的hK7蛋白降解。HK7在表达大量Dsg2的BxPC-3细胞中的表达增强，导致可溶性Dsg2的脱落明显增加，这与胰腺肿瘤hK7的异常表达可能导致细胞间黏附减少，促进肿瘤细胞侵袭的观点一致。
In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (KLK7/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells. The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using in vitro degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2. The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells. A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using in vitro degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion.
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影响因子：
6.2
作者：
Johnson, Sarah K.;Rarnani, Vishnu C.;Haun, Randy S.
通讯作者：
Haun, Randy S.
DOI：
10.1016/j.bbrc.2005.02.100
发表时间：
2005-04-22
影响因子：
3.1
作者：
Planque, C;de Monte, M;Courty, Y
通讯作者：
Courty, Y
DOI：
10.1016/j.bbrc.2008.03.021
发表时间：
2008-05-16
影响因子：
3.1
作者：
Ramani, Vishnu C.;Haun, Randy S.
通讯作者：
Haun, Randy S.
影响因子：
3.6
作者：
Mahoney, MG;Simpson, A;Pulkkinen, L
通讯作者：
Pulkkinen, L
DOI：
10.1083/jcb.138.1.193
发表时间：
1997-07-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chitaev NA;Troyanovsky SM
通讯作者：
Troyanovsky SM