Ets-1 positively regulates expression of urokinase-type plasminogen activator (uPA) and invasiveness of astrocytic tumors.
Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. Urokinase-type plasminogen activator (uPA) is often expressed in human tumors including astrocytic tumors. To elucidate the possible regulation mechanism of uPA gene expression in astrocytic tumors, quantitative RT-PCR was performed to monitor the gene expression of uPA and the transcription factor Ets-1. Expression of uPA and Ets-1 genes was up-regulated in astrocytic tumors, but was not detected in normal brain. Expression levels of uPA correlated with those of Ets-1, and also with the degree of malignancy of the tumors. Glioma cell lines U251, U87, and T98G also expressed both uPA and Ets-1 genes. Expression of a dominant negative mutant of Ets-1, which competitively inhibits Ets-1 function, abolished uPA expression in U251 cells. Parental U251 cells showed invasive growth in 3-dimensional collagen gel, however, cells expressing dominant negative Ets-1 failed to grow invasively in the collagen gel. Treatment of U251 cells with the uPA inhibitor aprotinin also inhibited spreading of cells into collagen gel. These results suggest that Ets-1 plays an essential role in regulation of uPA gene expression, which in turn contributes to the invasive growth of astrocytic tumors.
Nakada
M
M
Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Ishikawa, Japan.
Yamashita
J
J
Okada
Y
Y
Sato
H
H
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D015342:DNA Probes; D004273:DNA, Neoplasm; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D014568:Urokinase-Type Plasminogen Activator