Latent transforming growth factor binding protein 4 (LTBP4) is downregulated in mouse and human DCIS and mammary carcinomas
Latent transforming growth factor binding protein 4 (LTBP4) is downregulated in mouse and human DCIS and mammary carcinomas
Transforming growth factor beta (TGF-ß) is able to inhibit the proliferation of epithelial cells and is involved in the carcinogenesis of mammary tumors. Three latent transforming growth factor-ß binding proteins (LTBPs) are known to modulate TGF-ß functions.The current study analyses the expression profiles of LTBP4, its isoforms LTBP1 and LTBP3, and TGF-ß1, TGF-ß2, TGF-ß3, and SMAD2, SMAD3 and SMAD4 in human and murine (WAP-TNP8) DCIS compared to invasive mammary tumors. Additionally mammary malignant (MCF7, Hs578T, MDA-MB361) and non malignant cell lines (Hs578BsT) were analysed. Microarray, q-PCR, immunoblot, immunohistochemistry and immunofluorescence were used.In comparison to non-malignant tissues (n = 5), LTBP4 was downregulated in all human and mouse DCIS (n = 9) and invasive mammary adenocarcinomas (n = 5) that were investigated. We also found decreased expression of bone morphogenic protein 4 (BMP4) and increased expression of its inhibitor gremlin (GREM1). Treatment of the mammary tumor cell line (Hs578T) with recombinant TGF-ß1 rescued BMP4 and GREM1 expression.We conclude that the lack of LTBP4-mediated targeting in malignant mammary tumor tissues may lead to a possible modification of TGF-ß1 and BMP bioavailability and function.
- University of Cologne Germany
- Charité - University Medicine Berlin Germany
Cancer Research, Down-Regulation, Breast Neoplasms, Mammary Neoplasms, Animal, Bone Morphogenetic Protein 4, Mice, Cell Line, Tumor, Animals, Humans, Protein Isoforms, Phosphorylation, Medicine(all), Original Paper, Carcinoma, Ductal, Breast, Epithelial Cells, Immunohistochemistry, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Carcinoma, Intraductal, Noninfiltrating, Latent TGF-beta Binding Proteins, Cytokines, Intercellular Signaling Peptides and Proteins, Female
Cancer Research, Down-Regulation, Breast Neoplasms, Mammary Neoplasms, Animal, Bone Morphogenetic Protein 4, Mice, Cell Line, Tumor, Animals, Humans, Protein Isoforms, Phosphorylation, Medicine(all), Original Paper, Carcinoma, Ductal, Breast, Epithelial Cells, Immunohistochemistry, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Carcinoma, Intraductal, Noninfiltrating, Latent TGF-beta Binding Proteins, Cytokines, Intercellular Signaling Peptides and Proteins, Female
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