Abstract
Originalsprog | Engelsk |
---|---|
Tidsskrift | Molecular and Cellular Biology |
Vol/bind | 18 |
Udgave nummer | 12 |
Sider (fra-til) | 7095-7105 |
Antal sider | 10 |
ISSN | 0270-7306 |
Status | Udgivet - 1998 |
Bibliografisk note
Keywords: Adenocarcinoma; Animals; Cell Movement; DNA-Binding Proteins; Doxycycline; Gene Expression Regulation, Neoplastic; Genes, Reporter; Mice; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Nuclear Proteins; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Transcription Factor AP-1; Transcription, Genetic; Transfection; Tumor Cells, CulturedCitationsformater
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I: Molecular and Cellular Biology, Bind 18, Nr. 12, 1998, s. 7095-7105.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Fra-1 induces morphological transformation and increases in vitro invasiveness and motility of epithelioid adenocarcinoma cells
AU - Kustikova, O.
AU - Kramerov, D.
AU - Grigorian, M.
AU - Berezin, Vladimir
AU - Bock, Elisabeth Marianne
AU - Lukanidin, E.
AU - Tulchinsky, E.
N1 - Keywords: Adenocarcinoma; Animals; Cell Movement; DNA-Binding Proteins; Doxycycline; Gene Expression Regulation, Neoplastic; Genes, Reporter; Mice; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Nuclear Proteins; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Transcription Factor AP-1; Transcription, Genetic; Transfection; Tumor Cells, Cultured
PY - 1998
Y1 - 1998
N2 - Two cell lines originating from a common ancestral tumor, CSML0 and CSML100, were used as a model to study AP-1 transcription factors at different steps of tumor progression. CSML0 cells have an epithelial morphology; they express epithelial but not mesenchymal markers and are invasive neither in vitro nor in vivo. CSML100 possesses all characteristics of a highly progressive carcinoma. These cells do not form tight contacts, are highly invasive in vitro, and are metastatic in vivo. AP-1 activity was considerably higher in CSML100 cells than in CSML0 cells. There was a common predominant Jun component, namely, JunD, detected in both cell lines. We found that the enhanced level of AP-1 in CSML100 cells was due to high expression of Fra-1 and Fra-2 proteins, which were undetectable in CSML0 nuclear extracts. Analysis of the transcription of different AP-1 members in various cell lines derived from tumors of epithelial origin revealed a correlation of fra-1 expression with mesenchymal characteristics of carcinoma cells. Moreover, we show here for the first time that the expression of exogenous Fra-1 in epithelioid cells results in morphological changes that resemble fibroblastoid conversion. Cells acquire an elongated shape and become more motile and invasive in vitro. Morphological alterations were accompanied by transcriptional activation of certain genes whose expression is often induced at late stages of tumor progression. These data suggest a critical role of the Fra-1 protein in the development of epithelial tumors.
AB - Two cell lines originating from a common ancestral tumor, CSML0 and CSML100, were used as a model to study AP-1 transcription factors at different steps of tumor progression. CSML0 cells have an epithelial morphology; they express epithelial but not mesenchymal markers and are invasive neither in vitro nor in vivo. CSML100 possesses all characteristics of a highly progressive carcinoma. These cells do not form tight contacts, are highly invasive in vitro, and are metastatic in vivo. AP-1 activity was considerably higher in CSML100 cells than in CSML0 cells. There was a common predominant Jun component, namely, JunD, detected in both cell lines. We found that the enhanced level of AP-1 in CSML100 cells was due to high expression of Fra-1 and Fra-2 proteins, which were undetectable in CSML0 nuclear extracts. Analysis of the transcription of different AP-1 members in various cell lines derived from tumors of epithelial origin revealed a correlation of fra-1 expression with mesenchymal characteristics of carcinoma cells. Moreover, we show here for the first time that the expression of exogenous Fra-1 in epithelioid cells results in morphological changes that resemble fibroblastoid conversion. Cells acquire an elongated shape and become more motile and invasive in vitro. Morphological alterations were accompanied by transcriptional activation of certain genes whose expression is often induced at late stages of tumor progression. These data suggest a critical role of the Fra-1 protein in the development of epithelial tumors.
M3 - Journal article
C2 - 9819396
SN - 0270-7306
VL - 18
SP - 7095
EP - 7105
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 12
ER -