Involvement of Ets‐related proteins in hormone‐independent mammary cell‐specific gene expression

Thomas WELTE, Katja GARIMORTH, Sonja PHILIPP, Patricia JENNEWEIN, Carmen HUCK, Andrew C.B. CATO, Wolfgang DOPPLER

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Regulatory regions have been located in the 5′ flanking sequence of the mouse whey acidic protein gene which contribute to its tissue‐ and stage‐specific expression in the mammary gland. They can be functionally separated into elements which mediate the action of lactogenic hormones prolactin and glucocoticoids and elements which control mammary cell‐specific transcription in the absence of hormones. By mutational analysis, we have located a site in the whey acidic protein promoter between – 120 and – 100 which is important for hormone‐independent promoter function. In stably transfected HC11 mammary epithelial cells, the hormone‐independent activity of the mutated promoter was reduced 40‐fold, whereas the capability to respond to lactogenic hormones was retained. The site was specifically recognised by two nuclear factors contained in extracts of cultivated mammary epithelial cells or mammary glands. Electrophoretic mobility shift assay, DNase I footprinting and methylation interference experiments indicated a relation of both factors to the Ets family of DNA‐binding proteins. One of these factors also recognised a functionally important site in the mammary cell‐specific enhancer of the mouse mammary tumor virus long terminal repeat. The results suggest that factors related to the Ets family are important determinants in mammary cell‐specific gene expression.

Original languageEnglish (US)
Pages (from-to)997-1006
Number of pages10
JournalEuropean Journal of Biochemistry
Volume223
Issue number3
DOIs
StatePublished - Aug 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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