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

Jung, Y.; Abdel-Fatah, T.M.A.; Chan, S.Y.T.; Nolan, C.C.; Green, A.R.; Ellis, I.O.; Li, L.; Huang, B.; Lu, J.; Xu, B.; Chen, L.; Ma, R.Z.; Zhang, M.; Wang, J.; Wu, Z.; Zhu, T.; Perry, J.K.; Lobie, P.E.; Liu, D.-X.

Authors

Y. Jung

T.M.A. Abdel-Fatah

S.Y.T. Chan

C.C. Nolan

L. Li

B. Huang

J. Lu

B. Xu

L. Chen

R.Z. Ma

M. Zhang

J. Wang

Z. Wu

T. Zhu

J.K. Perry

P.E. Lobie

D.-X. Liu



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. Cancer Res; 73(23); 6951–62. ©2013 AACR.

Journal Article Type Article
Publication Date Dec 1, 2013
Journal Cancer Research
Print ISSN 0008-5472
Electronic ISSN 1538-7445
Publisher American Association for Cancer Research
Peer Reviewed Peer Reviewed
Volume 73
Issue 23
Pages 6951-6962
APA6 Citation Jung, Y., Abdel-Fatah, T., Chan, S., Nolan, C., Green, A., Ellis, I., …Liu, D. (2013). SHON Is a novel estrogen-regulated oncogene in mammary carcinoma that predicts patient response to endocrine therapy. Cancer Research, 73(23), 6951-6962. doi:10.1158/0008-5472.can-13-0982
DOI https://doi.org/10.1158/0008-5472.can-13-0982
Publisher URL http://cancerres.aacrjournals.org/content/73/23/6951
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