Ets-1 positively regulates expression of urokinase-type plasminogen activator (uPA) and invasiveness of astrocytic tumors

Mitsutoshi Nakada, Junkoh Yamashita, Yasunori Okada, Hiroshi Sato

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)329-334
Number of pages6
JournalJournal of Neuropathology and Experimental Neurology
Volume58
Issue number4
DOIs
Publication statusPublished - 1999 Apr
Externally publishedYes

Keywords

  • Astrocytic tumor
  • Ets-1
  • Invasion
  • uPA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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