Latent transforming growth factor binding protein 4 LTBP4 is downregulated in mouse and human DCIS and mammary carcinomasReportar como inadecuado




Latent transforming growth factor binding protein 4 LTBP4 is downregulated in mouse and human DCIS and mammary carcinomas - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cellular Oncology

, Volume 34, Issue 5, pp 419–434

First Online: 06 April 2011Accepted: 13 March 2011DOI: 10.1007-s13402-011-0023-y

Cite this article as: Kretschmer, C., Conradi, A., Kemmner, W. et al. Cell Oncol. 2011 34: 419. doi:10.1007-s13402-011-0023-y

Abstract

BackgroundTransforming 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.

MethodsThe 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.

ResultsIn 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.

ConclusionWe 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.

KeywordsLTBP4 TGF-ß DCIS Mammary carcinoma Carcinogenesis Tumour suppressor gene Electronic supplementary materialThe online version of this article doi:10.1007-s13402-011-0023-y contains supplementary material, which is available to authorized users.

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Autor: Celine Kretschmer - Anne Conradi - Wolfgang Kemmner - Anja Sterner-Kock

Fuente: https://link.springer.com/







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