Latent transforming growth factor binding protein 4 (LTBP-4) is downregulated in human mammary adenocarcinomas in vitro and in vivo.
Transforming growth factor beta (TGF-ss) is able to inhibit proliferation of epithelial cells and is involved in the carcinogenesis of human mammary tumours. Three latent transforming growth factor-beta binding proteins (LTBP-1, -3 and -4) are involved in TGF-beta function. The aim of the study was to analyze the expression profiles of TGF-beta 1 and 2 and LTBP-4 in human mammary carcinoma cell lines as well as in human mammary tumours. Expression analysis was performed at the transcription and protein level under in vivo and in vitro conditions. LTBP-4 expression was quantitatively analysed in human carcinomas of the mammary gland and in healthy mammary tissues of the same patients. Downregulation of LTBP-4 in all investigated human mammary tumours compared to normal tissues could be demonstrated. Results also revealed that protein levels of TGF-beta 1 are downregulated and of TGF-beta 2 are upregulated in human mammary carcinoma cell lines compared to primary (normal) human mammary epithelial cells. LTBP-4 reduction in neoplasms leads to a possible decrease of TGF-beta 1 extracellular deposition with reduced TGF-beta 1 bioavailability. TGF-beta 2 was upregulated, which indicates a possible compensatory mechanism. This study demonstrated a possible functional role of LTBP-4 for TGF-beta bioavailability with respect to carcinogenesis of human mammary tumours in vivo and in vitro.
Mauel
Susanne
S
Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
Kruse
Bianca
B
Etschmann
Benjamin
B
von der Schulenburg
Annabelle Gräfin
AG
Schaerig
Monika
M
Stövesand
Kirsten
K
Wilcken
Björn
B
Sterner-Kock
Anja
A
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053779:Latent TGF-beta Binding Proteins / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured
C509040:LTBP4 protein, human; D053779:Latent TGF-beta Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta