Abstract
The regulatory mechanisms underlying the overexpression of urokinase- type plasminogen activator (uPA) and its receptor (uPAR) in highly invasive breast carcinomas remain poorly understood. In this study, we have simultaneously determined the level of uPAR and the activity of the transcription factor Sp1 in 14 breast carcinomas and 5 benign lesions. We found that uPAR levels and Sp1-binding activity are coordinately elevated in malignant tumors (r, 0.94; P <0.001). On the contrary, undetectable or only barely detectable levels of uPAR and Sp1 activity were found in benign breast lesions. Finally, the engagement of uPAR by catalytically inactive uPA in the MDA-MB-231 breast carcinoma cell line results in a rapid up-regulation of Sp1-binding activity followed by an increase of uPAR protein. These results, taken together, suggest the existence of a uPA-dependent positive regulatory loop that may progressively enhance malignant breast cell invasiveness.
| Original language | English |
|---|---|
| Pages (from-to) | 1546-1551 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 60 |
| Issue number | 6 |
| Publication status | Published - Mar 15 2000 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma. / Zannetti, Antonella; Del Vecchio, Silvana; Carriero, Maria V.; Fonti, Rosa; Franco, Paola; Botti, Gerardo; D'Aiuto, Giuseppe; Stoppelli, M. Patrizia; Salvatore, Marco.
In: Cancer Research, Vol. 60, No. 6, 15.03.2000, p. 1546-1551.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma
AU - Zannetti, Antonella
AU - Del Vecchio, Silvana
AU - Carriero, Maria V.
AU - Fonti, Rosa
AU - Franco, Paola
AU - Botti, Gerardo
AU - D'Aiuto, Giuseppe
AU - Stoppelli, M. Patrizia
AU - Salvatore, Marco
PY - 2000/3/15
Y1 - 2000/3/15
N2 - The regulatory mechanisms underlying the overexpression of urokinase- type plasminogen activator (uPA) and its receptor (uPAR) in highly invasive breast carcinomas remain poorly understood. In this study, we have simultaneously determined the level of uPAR and the activity of the transcription factor Sp1 in 14 breast carcinomas and 5 benign lesions. We found that uPAR levels and Sp1-binding activity are coordinately elevated in malignant tumors (r, 0.94; P <0.001). On the contrary, undetectable or only barely detectable levels of uPAR and Sp1 activity were found in benign breast lesions. Finally, the engagement of uPAR by catalytically inactive uPA in the MDA-MB-231 breast carcinoma cell line results in a rapid up-regulation of Sp1-binding activity followed by an increase of uPAR protein. These results, taken together, suggest the existence of a uPA-dependent positive regulatory loop that may progressively enhance malignant breast cell invasiveness.
AB - The regulatory mechanisms underlying the overexpression of urokinase- type plasminogen activator (uPA) and its receptor (uPAR) in highly invasive breast carcinomas remain poorly understood. In this study, we have simultaneously determined the level of uPAR and the activity of the transcription factor Sp1 in 14 breast carcinomas and 5 benign lesions. We found that uPAR levels and Sp1-binding activity are coordinately elevated in malignant tumors (r, 0.94; P <0.001). On the contrary, undetectable or only barely detectable levels of uPAR and Sp1 activity were found in benign breast lesions. Finally, the engagement of uPAR by catalytically inactive uPA in the MDA-MB-231 breast carcinoma cell line results in a rapid up-regulation of Sp1-binding activity followed by an increase of uPAR protein. These results, taken together, suggest the existence of a uPA-dependent positive regulatory loop that may progressively enhance malignant breast cell invasiveness.
UR - http://www.scopus.com/inward/record.url?scp=0034653737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034653737&partnerID=8YFLogxK
M3 - Article
C2 - 10749121
AN - SCOPUS:0034653737
VL - 60
SP - 1546
EP - 1551
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 6
ER -