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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 13/2017

01-12-2017 | Translational Research and Biomarkers

Expression of 3β-Hydroxysteroid Dehydrogenase Type 1 in Breast Cancer is Associated with Poor Prognosis Independent of Estrogen Receptor Status

Authors: Yuan-Ching Chang, MD, PhD, Chi-Kuan Chen, MD, Ming-Jen Chen, MD, PhD, Jiunn-Chang Lin, MD, PhD, Chi-Hsin Lin, PhD, Wen-Chien Huang, MD, PhD, Shih-Ping Cheng, MD, PhD, Shan-Na Chen, BSc, Chien-Liang Liu, MD

Published in: Annals of Surgical Oncology | Issue 13/2017

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Abstract

Background

Human 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings.

Methods

Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo.

Results

The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth.

Conclusions

Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.
Appendix
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Metadata
Title
Expression of 3β-Hydroxysteroid Dehydrogenase Type 1 in Breast Cancer is Associated with Poor Prognosis Independent of Estrogen Receptor Status
Authors
Yuan-Ching Chang, MD, PhD
Chi-Kuan Chen, MD
Ming-Jen Chen, MD, PhD
Jiunn-Chang Lin, MD, PhD
Chi-Hsin Lin, PhD
Wen-Chien Huang, MD, PhD
Shih-Ping Cheng, MD, PhD
Shan-Na Chen, BSc
Chien-Liang Liu, MD
Publication date
01-12-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 13/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-017-6000-6

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