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Clin Cancer Res. 2007 Nov 1;13(21):6327-34.

The prognostic biomarkers HOXB13, IL17BR, and CHDH are regulated by estrogen in breast cancer.

Author information

1
Department of Pathology, Harvard Medical School, Molecular Pathology Research Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

PURPOSE:

We previously identified three genes, HOXB13, IL17BR, and CHDH, that strongly predict clinical outcome in estrogen receptor (ER)-positive breast cancer patients receiving tamoxifen monotherapy. The biological mechanisms linking these genes to estrogen signaling and tamoxifen response in breast cancer remain to be determined.

EXPERIMENTAL DESIGN:

In a consecutive series of 148 ER-positive and ER-negative breast cancers, HOXB13, IL17BR, and CHDH gene expression was measured by quantitative real-time PCR and correlated with ER, PR, and HER2 expression. The role of estrogen and ER in the regulation of these three genes was assessed in several ER-positive and ER-negative breast cancer cell lines.

RESULTS:

In primary breast tumors, HOXB13 expression correlated negatively, and IL17BR and CHDH expression correlated positively, with ER status, and all three genes exhibited an ER-dependent correlation pattern with HER2 status that differs from PR and PS2, two canonical estrogen-regulated genes. Results using breast cancer cell lines show that these genes are regulated by estradiol in an ER-dependent manner, and that this regulation is abrogated by tamoxifen.

CONCLUSIONS:

HOXB13, IL17BR, and CHDH are estrogen-regulated genes, but their pattern of correlation with known positive (ER, PR) and negative (HER2) predictors of tamoxifen response differs from canonical ER signature genes. These results provide a biological rationale for the prognostic utility of these three genes in early-stage ER-positive breast cancer and for their potential to predict anti-estrogen resistance.

PMID:
17975144
DOI:
10.1158/1078-0432.CCR-07-0310
[Indexed for MEDLINE]
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