Transkriptionelle regulierung des protease-inhibitors maspin in brustepithel- und Brustkrebs-Zellen

Translated title of the contribution: Transcriptional regulation of protease-inhibitor Maspin in breast epithelial- and breast cancer-cellines

N. Maass*, M. Zhang, Ruth Sager, W. Jonat

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Maspin (mammary serpin) is a novel serine protease-inhibitor with tumor suppressor activity in human mammary epithelial cells. The maspin gene is expressed in normal mammary epithelial cells but down-regulated in a series of tumor derived breast cell lines. Maspin's decreased expression with increased level of malignancy and its loss in metastatic cells is regulated at the transcriptional level. Methods and Results: We have cloned and sequenced the maspin promoter region to investigate its regulation in normal and tumor cells. By chloramphenicol-transferase-(CAT) assay and deletion analysis the PEA-3 and AP-1 sites were identified within the maspin promoter that are active in regulating maspin expression, in normal mammary epithelial cells but inactive in tumor cells. The PEA-3 site alone is sufficient to activate transcription in a heterologous promoter, while the AP-1 site cooperates with PEA-3 in activation. The enhancing function by PEA-3 and AP- 1 promoter elements is decreased with malignancy (primary tumor cells 21NT) and is abolished in metastatic cells (MDA-MB231). Gel retardation experiments (EMSA) confirm the presence of PEA-3 binding proteins which differ qualitatively and quantitatively in a comparison of normal mammary epithelial cells and mammary carcinoma cells. Conclusions: Our data demonstrate that the loss of maspin expression during tumor progression is regulated at the transcriptional level and results most likely from the absence of transactivation through the PEA-3 and AP-1 sites. The study of the maspin promoter not only helps to understand the mechanism of gene regulation, but also offers an opportunity for reexpression of maspin in tumors by therapeutical intervention.

Translated title of the contributionTranscriptional regulation of protease-inhibitor Maspin in breast epithelial- and breast cancer-cellines
Original languageGerman
Pages (from-to)89-96
Number of pages8
JournalTumor Diagnostik und Therapie
Volume18
Issue number4
StatePublished - Oct 18 1997

Keywords

  • AP-1
  • Breast cancer
  • Maspin
  • PEA-3
  • Protease inhibitor
  • Transcription factors

ASJC Scopus subject areas

  • Oncology

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