PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer

Malavika G Ghosh; Devon A Thompson; Ronald J Weigel

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PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer

Journal article

Peer reviewed

PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer

Malavika G Ghosh, Devon A Thompson and Ronald J Weigel

Cancer research (Chicago, Ill.), Vol.60(22), pp.6367-6375

11/15/2000

PMID: 11103799

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Abstract

The function of estrogen in breast cancer proliferation and progression is likely to be due to the expression of a repertoire of genes regulated by estrogen receptor (ER). Using suppression subtractive hybridization, we have isolated a set of 14 estrogen-responsive genes that was differentially expressed in MCF7 cells stimulated by beta-estradiol as compared with unstimulated cells. Tamoxifen repressed the expression of all 14 estrogen-responsive genes. Thirteen of the genes were induced within 6 h of estrogen treatment, indicating that these were early response genes in the ER-regulated pathway. PDZK1 and a new gene, GREB1, demonstrated a significant correlation with ER phenotype in a panel of breast cancer cell lines. Treatment with cycloheximide indicated that ER directly controls GREB1 expression. Three cDNAs (GREB1a, GREB1b, and GREB1c) were isolated by screening a MCF7 cDNA library. These three cDNAs of GREB1 shared extensive sequences through the open reading frame but had divergent 5' untranslated regions, indicating the possibility of multiple promoters regulated by beta-estradiol. Studies in primary breast cancers showed that PDZK1 and GREB1 were overexpressed in ER-positive breast cancers as compared with ER-negative breast cancers by 19-fold and 3.5-fold, respectively. GREB1 was also induced by beta-estradiol in the ER-positive endometrial cell line ECC-1. The pattern of expression suggests a critical role for these two genes in the response of tissues and tumors to beta-estradiol.

Neoplasms, Hormone-Dependent - metabolism

Humans

DNA, Complementary - genetics

Molecular Sequence Data

Gene Expression Profiling

Breast Neoplasms - metabolism

Neoplasms, Hormone-Dependent - genetics

Time Factors

Base Sequence

Cloning, Molecular

Gene Expression Regulation, Neoplastic - drug effects

Tumor Cells, Cultured

Neoplasm Proteins - genetics

Gene Expression Regulation, Neoplastic - physiology

Estradiol - pharmacology

Estradiol - physiology

Amino Acid Sequence

Receptors, Estrogen - genetics

Membrane Proteins - genetics

Neoplasm Proteins - biosynthesis

Reverse Transcriptase Polymerase Chain Reaction

Estrogen Receptor Modulators - pharmacology

Membrane Proteins - biosynthesis

Breast Neoplasms - genetics

Tamoxifen - pharmacology

DNA, Neoplasm - genetics

Receptors, Estrogen - physiology

Details

Title: Subtitle: PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer
Creators: Malavika G Ghosh - Department of Surgery, Stanford University, California 94305, USA
Devon A Thompson
Ronald J Weigel
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.60(22), pp.6367-6375
Publisher: United States
PMID: 11103799
ISSN: 0008-5472
eISSN: 1538-7445
Grant note: R01-CA77350 / NCI NIH HHS
Language: English
Date published: 11/15/2000
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984025276302771

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