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- W2955266133 abstract "1774 Pleiotrophin (PTN, Ptn is the gene) is an 18 KDa heparin-binding cytokine. The Ptn gene is regulated both temporally and in cell type specificity during development but, in adults, Ptn gene expression is constitutive and limited to few cell types, except in inflammatory and endothelial cells in injured tissue and early tissue repair. The Ptn gene is an oncogene; Ptn expression is found in glioblastoma, breast cancer, melanoma and many other tumors. In these studies, we wished to identify the role of PTN in breast cancer. We generated transgenic mice in which the Ptn gene was driven by the mouse mammary tumor virus promoter (MMTV) and bred these mice with MMTV-Polyoma middle T (PyMT) gain of function breast cancer predisposition mice. The MMTV-Ptn gain of function mice breed and lactate normally and histological abnormalities in breast tissue have not been found. There is no significant difference in the onset of palpable tumors between MMTV-PyMT single transgenic mice and MMTV-PyMT/Ptn double transgenic mice; although the average tumor size in MMTV-PyMT/Ptn double transgenic mice was larger, the difference was not statistically significant. However, the morphological pattern of the MMTV-PyMT/Ptn double transgenic mice differed; we observed a significant increase of epithelial islands characteristic of invasive scirrhous carcinoma in areas within the tumor. The levels of expression of the Ptn gene were higher in these areas with a scirrhous carcinoma pattern. Furthermore, these areas were surrounded by collagen and elastin and increased numbers of new blood vessels were found in the microenvironment surrounding the tumors. Increased levels of activated ERK1/2 were found and the expression of ER1-46, the 46 KD isoform of Estrogen Receptor 1 that has lost the N-terminal estrogen-independent transactivation domain was also increased. These data support the conclusion that expression of Ptn initiates a significant switch to aggressive growth in MMTV-PyMT breast cancer in mice." @default.
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- W2955266133 date "2006-04-15" @default.
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- W2955266133 title "Expression of Ptn increases the areas of invasive scirrhous carcinoma in MMTV-PyMT transgenic mouse model of breast cancer" @default.
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