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 Min, C. Articles by Sonenshein, G. E. Search for Related Content PubMed PubMed Citation Articles by Min, C. Articles by Sonenshein, G. E.

The Tumor Suppressor Activity of the Lysyl Oxidase Propeptide Reverses the Invasive Phenotype of Her-2/neu–Driven Breast Cancer

¹ Department of Biochemistry, Boston University School of Medicine, and ² Division of Oral Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts

Requests for reprints: Gail E. Sonenshein, Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118. Phone: 617-638-4120; Fax: 617-638-4252; E-mail: gsonensh{at}bu.edu.

Expression of the lysyl oxidase gene (LOX) was found to inhibit the transforming activity of the ras oncogene in NIH 3T3 fibroblasts and was hence named the ras recision gene (rrg). Lysyl oxidase (LOX) is synthesized and secreted as a 50-kDa inactive proenzyme (Pro-LOX), which is processed by proteolytic cleavage to a functional 32-kDa enzyme and an 18-kDa propeptide (LOX-PP). Recently, the ras recision activity of the LOX gene in NIH 3T3 cells was mapped to its propeptide region. Here, we show for the first time that LOX-PP inhibits transformation of breast cancer cells driven by Her-2/neu, an upstream activator of Ras. LOX-PP expression in Her-2/neu–driven breast cancer cells in culture suppressed Akt, extracellular signal–regulated kinase, and nuclear factor-B activation. Her-2/neu–induced epithelial to mesenchymal transition was reverted by LOX-PP, as judged by reduced levels of Snail and vimentin; up-regulation of E-cadherin, -catenin, and estrogen receptor ; and decreased ability to migrate or to form branching colonies in Matrigel. Furthermore, LOX-PP inhibited Her-2/neu tumor formation in a nude mouse xenograft model. Thus, LOX-PP inhibits signaling cascades induced by Her-2/neu that promote a more invasive phenotype and may provide a novel avenue for treatment of Her-2/neu–driven breast carcinomas. [Cancer Res 2007;67(3):1105–12]

This article has been cited by other articles:

				T.-M. Shieh, S.-C. Lin, C.-J. Liu, S.-S. Chang, T.-H. Ku, and K.-W. Chang Association of Expression Aberrances and Genetic Polymorphisms of Lysyl Oxidase with Areca-Associated Oral Tumorigenesis Clin. Cancer Res., August 1, 2007; 13(15): 4378 - 4385. [Abstract] [Full Text] [PDF]

				M. Wu, C. Min, X. Wang, Z. Yu, K. H. Kirsch, P. C. Trackman, and G. E. Sonenshein Repression of BCL2 by the Tumor Suppressor Activity of the Lysyl Oxidase Propeptide Inhibits Transformed Phenotype of Lung and Pancreatic Cancer Cells Cancer Res., July 1, 2007; 67(13): 6278 - 6285. [Abstract] [Full Text] [PDF]