Downregulation of fibronectin transcription in highly metastatic adenocarcinoma cells

Silencing of fibronectin (FN) expression seems to be one of the key mechanisms underlying metastatic behaviour. An inverse correlation exists between FN expression levels and the metastatic potential of two related murine mammary adenocarcinomas, M3 and MM3. Primary cultures of M3 tumour, which is m...

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Bibliographic Details
Published in:FEBS letters 1998-12, Vol.440 (3), p.277-281
Main Authors: Werbajh, Santiago E, Urtreger, Alejandro J, Puricelli, Lydia I, de Lustig, Eugenia S, Bal de Kier Joffé, Elisa, Kornblihtt, Alberto R
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - secondary
Alternative Splicing
Animals
Chloramphenicol O-Acetyltransferase - genetics
Down-Regulation
Fibronectin
Fibronectins - genetics
Gene Expression Regulation, Neoplastic
Genes, Reporter
Mammary Neoplasms, Experimental - genetics
Mammary Neoplasms, Experimental - pathology
Metastasis
Mice
Mice, Inbred BALB C
Neoplasm Metastasis
Promoter Regions, Genetic
RNA, Messenger
Signal Transduction
Transcription
Transcription, Genetic
Tumor Cells, Cultured
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Summary:Silencing of fibronectin (FN) expression seems to be one of the key mechanisms underlying metastatic behaviour. An inverse correlation exists between FN expression levels and the metastatic potential of two related murine mammary adenocarcinomas, M3 and MM3. Primary cultures of M3 tumour, which is moderately metastatic to lung (40% incidence), show a conspicuous FN extracellular matrix (ECM) and high levels of FN mRNA, while primary cultures of the highly metastatic MM3 tumour (95% lung incidence) are negative for FN in immunofluorescence and show at least 40-fold lower levels of FN mRNA, only detectable by RT-PCR, with a different pattern of alternatively spliced EDI isoforms compared to M3 cells. We show that the FN promoter sequence is not altered in MM3 cells. Transfection experiments with CAT constructs indicate that silencing occurs at the transcriptional level, involving the 220-bp proximal promoter region.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(98)01473-2