PMID- 10749121 OWN - NLM STAT- MEDLINE DCOM- 20000504 LR - 20081121 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 60 IP - 6 DP - 2000 Mar 15 TI - Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma. PG - 1546-51 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. FAU - Zannetti, A AU - Zannetti A AD - Centro Medicina Nucleare, Consiglio Nazionale delle Ricerche, Dipartimento di Scienze Biomorfologiche e Funzionali, Universita Federico II, Naples, Italy. FAU - Del Vecchio, S AU - Del Vecchio S FAU - Carriero, M V AU - Carriero MV FAU - Fonti, R AU - Fonti R FAU - Franco, P AU - Franco P FAU - Botti, G AU - Botti G FAU - D'Aiuto, G AU - D'Aiuto G FAU - Stoppelli, M P AU - Stoppelli MP FAU - Salvatore, M AU - Salvatore M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (DNA-Binding Proteins) RN - 0 (Oligonucleotides) RN - 0 (PLAUR protein, human) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Urokinase Plasminogen Activator) RN - 0 (Sp1 Transcription Factor) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Blotting, Western MH - Breast/chemistry/pathology MH - Breast Neoplasms/*metabolism/pathology MH - DNA-Binding Proteins/metabolism MH - Female MH - HeLa Cells MH - Humans MH - Immunohistochemistry MH - Middle Aged MH - Oligonucleotides/metabolism MH - Protein Binding MH - Receptors, Cell Surface/*biosynthesis MH - Receptors, Urokinase Plasminogen Activator MH - Sp1 Transcription Factor/*metabolism MH - Tumor Cells, Cultured/drug effects/metabolism MH - Up-Regulation/drug effects MH - Urokinase-Type Plasminogen Activator/pharmacology EDAT- 2000/04/05 09:00 MHDA- 2000/05/08 09:00 CRDT- 2000/04/05 09:00 PHST- 2000/04/05 09:00 [pubmed] PHST- 2000/05/08 09:00 [medline] PHST- 2000/04/05 09:00 [entrez] PST - ppublish SO - Cancer Res. 2000 Mar 15;60(6):1546-51.