Protein tyrosine phosphatase PRL-3 in malignant cells and endothelial cells: expression and function

被引：53

作者：

Rouleau, C ^{[1
]}

Roy, A ^{[1
]}

St Martin, T ^{[1
]}

Dufault, MR ^{[1
]}

Boutin, P ^{[1
]}

Liu, DP ^{[1
]}

Zhang, M ^{[1
]}

Puorro-Radzwill, K ^{[1
]}

Rulli, L ^{[1
]}

Reczek, D ^{[1
]}

Bagley, R ^{[1
]}

Byrne, A ^{[1
]}

Weber, W ^{[1
]}

Roberts, B ^{[1
]}

Klinger, K ^{[1
]}

Brondyk, W ^{[1
]}

Nacht, M ^{[1
]}

Madden, S ^{[1
]}

Burrier, R ^{[1
]}

Shankara, S ^{[1
]}

Teicher, BA ^{[1
]}

机构：

[1] Genzyme Corp, Framingham, MA 01701 USA

来源：

MOLECULAR CANCER THERAPEUTICS | 2006年 / 5卷 / 02期

关键词：

D O I：

10.1158/1535-7163.MCT-05-0289

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Protein tyrosine phosphatase PRL-3 mRNA was found highly expressed in colon cancer endothelium and metastases. We sought to associate a function with PRL-3 expression in both endothelial cells and malignant cells using in vitro models. PRL-3 mRNA levels were determined in several normal human endothelial cells exposed or unexposed to the phorbol ester phorbol 12-myristate 13-acetate (PMA) and in 27 human tumor cell lines. In endothelial cells, PRL-3 mRNA expression was increased in human umbilical vascular endothelial cells and human microvascular endothelial cells (HMVEC) exposed to PMA. An oligonucleotide microarray analysis revealed that PRL-3 was among the 10 genes with the largest increase in expression on PMA stimulation. Phenotypically, PMA-treated HMVEC showed increased invasion, tube formation, and growth factor-stimulated proliferation. A flow cytometric analysis of cell surface markers showed that PMA-treated HMVEC retained endothelial characteristics. Infection of HMVEC with an adenovirus expressing PRL-3 resulted in increased tube formation. In tumor cells, PRL-3 mRNA levels varied markedly with high expression in SKNAS neuroblastoma, MCF-7 and BT474 breast carcinoma, Hep3B hepatocellular carcinoma, and HCT116 colon carcinoma. Western blotting analysis of a subset of cell line lysates showed a positive correlation between PRL-3 mRNA and protein levels. PRL-3 was stably transfected into DLD-1 colon cancer cells. PRL-3-overexpressing DLD-1 subclones were assessed for doubling time and invasion. Although doubling time was similar among parental, empty vector, and PRL-3 subclones, invasion was increased in PRL-3-expressing subclones. In models of endogenous expression, we observed that the MCF-7 cell line, which expresses high levels of PRL-3, was more invasive than the SKBR3 cell line, which expresses low levels of PRL-3. However, the MDA-MB-231 cell line was highly invasive with low levels of PRL-3, suggesting that in some models invasion is PRL-3 independent. Transfection of a PRL-3 small interfering RNA into MCF-7 cells inhibited PRL-3 expression and cell invasion. These results indicate that PRL-3 is functional in both endothelial cells and malignant cells and further validate PRL-3 as a potentially important molecular target for anticancer therapy.

引用

页码：219 / 229

页数：11

共 53 条

[1] CONTROLLED SYNTHESIS OF HBSAG IN A DIFFERENTIATED HUMAN-LIVER CARCINOMA-DERIVED CELL-LINE [J].