Identification of a functional imperfect estrogen-responsive element in the 5'-promoter region of the human cathepsin D gene

F. Wang, W. Porter, W. Xing, T. K. Archer, S. Safe

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

17β-Estradiol (E2) induces cathepsin D gene expression in MCF-7 human breast cancer cells. Previous studies have identified an Sp1-imperfect estrogen-responsive element (ERE) half-site [GGGCGG(N)23ACGGG] (-199 to - 165) in the promoter region which forms an Sp1-estrogen receptor (ER) complex and confers E2 responsiveness on the corresponding Sp1-ERE-chloramphenicol acetyl transferase (CAT) construct. Further analysis of downstream regions of the promoter identified a CGCCC-(N)3TGACC sequence (-119 to -107) which is homologous to the adenovirus major late promoter element (MLPE) and binds the ER to form a retarded band in a gel electrophoretic mobility shift assay. The corresponding promoter-CAT construct is also E2-inducible. The MLPE resembles an imperfect palindromic ERE containing imperfect (5') and perfect (3') ERE half-sites; analysis of oligonucleotides with mutations in these half-sites shows that only the perfect ERE half-site is required for binding the ER, whereas both sites are required for transactivation. In vivo exonuclease III footprinting showed that treatment with E2 also enhanced binding at the MLPE site. Identification of this second functional enhancer sequence in the 5'- promoter region of cathepsin D is consistent with the increasingly complex cell-specific regulation of hormone-responsive genes.

Original languageEnglish (US)
Pages (from-to)7793-7801
Number of pages9
JournalBiochemistry
Volume36
Issue number25
DOIs
StatePublished - Jun 24 1997

ASJC Scopus subject areas

  • Biochemistry

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