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

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.

• Authors: Yewon Jung, Tarek M A Abdel-Fatah, Stephen Y T Chan, Christopher C Nolan, Andrew R Green, Ian O Ellis, Lili Li, Baiqu Huang, Jun Lu, Bing Xu, Longxin Chen, Runlin Z Ma, Min Zhang, Jingru Wang, ZhengSheng Wu, Tao Zhu, Jo K Perry, Peter E Lobie, Dong-Xu Liu
• Journal: Cancer research (Cancer Res) Vol. 73 Issue 23 Pg. 6951-62 (Dec 01 2013) ISSN: 1538-7445 [Electronic] United States
• PMID: 24296488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Biomarkers, Pharmacological
• Estrogen Receptor Modulators
• Estrogens
• Oncogene Proteins
• SHON protein, human

Topics

• Animals
• Antineoplastic Agents, Hormonal (therapeutic use)
• Biomarkers, Pharmacological
• Breast Neoplasms (diagnosis, drug therapy, genetics)
• Estrogen Receptor Modulators (therapeutic use)
• Estrogens (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• HEK293 Cells
• Humans
• MCF-7 Cells
• Mice
• Mice, Nude
• Oncogene Proteins (genetics, physiology)
• Oncogenes (physiology)
• Prognosis
• Treatment Outcome