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Cancer Res. 2013 Dec 1;73(23):6951-62. doi: 10.1158/0008-5472.CAN-13-0982.

SHON is a novel estrogen-regulated oncogene in mammary carcinoma that predicts patient response to endocrine therapy.

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1
Authors' Affiliations: Liggins Institute, University of Auckland, Auckland, New Zealand; Department of Clinical Oncology; Department of Histopathology, School of Molecular Medical Sciences, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University; The Institute of Genetics and Cytology, Northeast Normal University, Changchun; Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing; Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China; Department of Pathology, Anhui Medical University, Hefei, China; Cancer Science Institute of Singapore, and Department of Pharmacology, National University of Singapore; and National Cancer Institute of Singapore, National University Health System, Singapore.

Abstract

Endocrine therapies are the primary systemic intervention for patients with estrogen receptor-positive (ER(+)) breast cancer. However, a significant proportion of initially responsive ER(+) tumors develop resistance, with relapses occurring in up to 50% of patients. Lack of reliable predictive biomarkers remains an unfilled need for enhanced clinical management of this disease. In this study, we address this need in identifying a novel estrogen-regulated gene called SHON (secreted hominoid-specific oncogene). Enforced expression of SHON in breast cancer cells increased their proliferation, survival, migration, and invasion in vitro. Furthermore, SHON enhanced the oncogenicity of these cells in xenograft models of human breast cancer and was also sufficient to oncogenically transform MCF10A human mammary epithelial cells. Conversely, SHON attenuation mediated by RNA interference- or antibody-based methods reduced the oncogenicity of breast cancer cells. Mechanistic investigations indicated that the oncogenic transforming properties of SHON were mediated by BCL-2 and NF-κB. In primary clinical specimens, SHON was immunohistochemically detected in 62% of breast cancers, in which its expression was positively correlated with ER expression. In this setting, SHON expression predicted a favorable response to endocrine therapy in high-risk patients with ER(+) breast cancer. Taken together, our findings identify SHON as a novel human oncogene with predictive utility in ER(+) breast cancer, perhaps offering a simple biomarker to predict the therapeutic efficacy of antiestrogen therapy in patients with breast cancer.

PMID:
24296488
DOI:
10.1158/0008-5472.CAN-13-0982
[Indexed for MEDLINE]
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