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Latent transforming growth factor binding protein 4 (LTBP4) is downregulated in mouse and human DCIS and mammary carcinomas

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Item Type:Article
Title:Latent transforming growth factor binding protein 4 (LTBP4) is downregulated in mouse and human DCIS and mammary carcinomas
Creators Name:Kretschmer, C. and Conradi, A. and Kemmner, W. and Sterner-Kock, A.
Abstract:BACKGROUND: Transforming growth factor beta (TGF-beta) is able to inhibit the proliferation of epithelial cells and is involved in the carcinogenesis of mammary tumors. Three latent transforming growth factor-beta binding proteins (LTBPs) are known to modulate TGF-beta functions. METHODS: The current study analyses the expression profiles of LTBP4, its isoforms LTBP1 and LTBP3, and TGF-beta1, TGF-beta2, 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. RESULTS: 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-beta1 rescued BMP4 and GREM1 expression. CONCLUSION: We conclude that the lack of LTBP4-mediated targeting in malignant mammary tumor tissues may lead to a possible modification of TGF-beta1 and BMP bioavailability and function.
Keywords:LTBP4, TGF-beta, DCIS, Mammary Carcinoma, Carcinogenesis, Tumour Suppressor Gene, Animals, Mice
Source:Cellular Oncology
Publisher:Springer (The Netherlands)
Page Range:419-434
Date:6 October 2011
Official Publication:https://doi.org/10.1007/s13402-011-0023-y
PubMed:View item in PubMed

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