This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rouleau, C. Articles by Teicher, B. A. Search for Related Content PubMed PubMed Citation Articles by Rouleau, C. Articles by Teicher, B. A.

Genzyme Corp., Framingham, Massachusetts

Requests for reprints: Beverly A. Teicher, Genzyme Corp., 1 Mountain Road, Framingham, MA 01701. Phone: 508-271-2843; Fax: 508-620-1203. E-mail: Beverly.Teicher{at}Genzyme.com

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. [Mol Cancer Ther 2006;5(2):219–29]

Received 7/29/05; revised 10/19/05; accepted 12/ 7/05.

This article has been cited by other articles:

				F. Liang, Y. Luo, Y. Dong, C. D. Walls, J. Liang, H.-Y. Jiang, J. R. Sanford, R. C. Wek, and Z.-Y. Zhang Translational Control of C-terminal Src Kinase (Csk) Expression by PRL3 Phosphatase J. Biol. Chem., April 18, 2008; 283(16): 10339 - 10346. [Abstract] [Full Text] [PDF]

				S. Daouti, W.-h. Li, H. Qian, K.-S. Huang, J. Holmgren, W. Levin, L. Reik, D. L. McGady, P. Gillespie, A. Perrotta, et al. A Selective Phosphatase of Regenerating Liver Phosphatase Inhibitor Suppresses Tumor Cell Anchorage-Independent Growth by a Novel Mechanism Involving p130Cas Cleavage Cancer Res., February 15, 2008; 68(4): 1162 - 1169. [Abstract] [Full Text] [PDF]

				U.-M. Fagerli, R. U. Holt, T. Holien, T. K. Vaatsveen, F. Zhan, K. W. Egeberg, B. Barlogie, A. Waage, H. Aarset, H. Y. Dai, et al. Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells Blood, January 15, 2008; 111(2): 806 - 815. [Abstract] [Full Text] [PDF]

				B. Stephens, H. Han, G. Hostetter, M. J. Demeure, and D. D. Von Hoff Small interfering RNA-mediated knockdown of PRL phosphatases results in altered Akt phosphorylation and reduced clonogenicity of pancreatic cancer cells Mol. Cancer Ther., January 1, 2008; 7(1): 202 - 210. [Abstract] [Full Text] [PDF]

				J.-P. Sun, Y. Luo, X. Yu, W.-Q. Wang, B. Zhou, F. Liang, and Z.-Y. Zhang Phosphatase Activity, Trimerization, and the C-terminal Polybasic Region Are All Required for PRL1-mediated Cell Growth and Migration J. Biol. Chem., September 28, 2007; 282(39): 29043 - 29051. [Abstract] [Full Text] [PDF]

				F. Liang, J. Liang, W.-Q. Wang, J.-P. Sun, E. Udho, and Z.-Y. Zhang PRL3 Promotes Cell Invasion and Proliferation by Down-regulation of Csk Leading to Src Activation J. Biol. Chem., February 23, 2007; 282(8): 5413 - 5419. [Abstract] [Full Text] [PDF]

				K. Guo, J. Li, H. Wang, M. Osato, J. P. Tang, S. Y. Quah, B. Q. Gan, and Q. Zeng PRL-3 Initiates Tumor Angiogenesis by Recruiting Endothelial Cells In vitro and In vivo Cancer Res., October 1, 2006; 66(19): 9625 - 9635. [Abstract] [Full Text] [PDF]