The Prognostic Biomarkers HOXB13, IL17BR, and CHDH Are Regulated by Estrogen in Breast Cancer
- 1 November 2007
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 13 (21) , 6327-6334
- https://doi.org/10.1158/1078-0432.ccr-07-0310
Abstract
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. 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. 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. 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.Keywords
This publication has 25 references indexed in Scilit:
- HOXB13-to-IL17BR Expression Ratio Is Related With Tumor Aggressiveness and Response to Tamoxifen of Recurrent Breast Cancer: A Retrospective StudyJournal of Clinical Oncology, 2007
- The HOXB13:IL17BR Expression Index Is a Prognostic Factor in Early-Stage Breast CancerJournal of Clinical Oncology, 2006
- Genome-wide analysis of estrogen receptor binding sitesNature Genetics, 2006
- A Two-Gene Expression Ratio of Homeobox 13 and Interleukin-17B Receptor for Prediction of Recurrence and Survival in Women Receiving Adjuvant TamoxifenClinical Cancer Research, 2006
- Gene Expression Profiling in Breast Cancer: Understanding the Molecular Basis of Histologic Grade To Improve PrognosisJNCI Journal of the National Cancer Institute, 2006
- Re: Limits of predictive models using microarray data for breast cancer clinical treatment outcome.JNCI Journal of the National Cancer Institute, 2005
- A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast CancerNew England Journal of Medicine, 2004
- Gene Expression Signature of Fibroblast Serum Response Predicts Human Cancer Progression: Similarities between Tumors and WoundsPLoS Biology, 2004
- Gene expression profiling predicts clinical outcome of breast cancerNature, 2002
- Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implicationsProceedings of the National Academy of Sciences, 2001