lysyl oxidase propeptide reverses the invasive phenotype of Her-2/neu-driven breast c

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http://www.newsrx.com/articles/485043.htmlScientists at Boston University, Department of Biochemistry release new data on breast cancer

United States
Boston
Breast Cancer
Breast Carcinoma
Cancer Research
Oncology
Peptide
Proteins
Proteomics
Women's Health
(NewsRx.com) -- Researchers detail in "The tumor suppressor activity of the lysyl oxidase propeptide reverses the invasive phenotype of Her-2/neu-driven breast cancer," new data in breast cancer. According to recent research from the United States, "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-kappaB 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, gamma-catenin, and estrogen receptor alpha; 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," wrote C. Min and colleagues, Boston University, Department of Biochemistry.

The researchers concluded: "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."

Min and colleagues published their study in Cancer Research (The tumor suppressor activity of the lysyl oxidase propeptide reverses the invasive phenotype of Her-2/neu-driven breast cancer. Cancer Research, 2007;67(3):1105-12). For additional information, contact C. Min, Boston University School of Medicine, Dept. of Biochemistry, 715 Albany Street, Boston, MA 02118 USA.