Yuan-Ching Chang1,2,3, Chi-Kuan Chen4, Ming-Jen Chen1,2, Jiunn-Chang Lin1,2,3, Chi-Hsin Lin2,5, Wen-Chien Huang1,2, Shih-Ping Cheng1,2, Shan-Na Chen2, Chien-Liang Liu6,7,8. 1. Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan. 2. Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan. 3. Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan. 4. Department of Pathology, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan. 5. Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan City, Taiwan. 6. Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan. changyc@mmh.org.tw. 7. Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan. changyc@mmh.org.tw. 8. Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan. changyc@mmh.org.tw.
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.
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 cancerpatients 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.
Authors: Meghan R Flanagan; David R Doody; Jenna Voutsinas; Qian Wu; Kalyan Banda; Nima Sharifi; Christopher I Li; Vijayakrishna K Gadi Journal: Ann Surg Oncol Date: 2022-07-01 Impact factor: 4.339