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Open AccessArticle

SET Overexpression is Associated with Worse Recurrence-Free Survival in Patients with Primary Breast Cancer Receiving Adjuvant Tamoxifen Treatment

1
School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
2
Department of Pathology, Show Chwan Memorial Hospital, Changhua City 50091, Taiwan
3
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan
4
Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei 11217, Taiwan
5
Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
6
Division of Hematology & Oncology, Department of Medicine, Yang-Ming Branch of Taipei City Hospital, Taipei 11221, Taiwan
7
Division of Experimental Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan
8
Department of Nursing, Taipei Veterans General Hospital, Taipei 11217, Taiwan
9
Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2018, 7(9), 245; https://doi.org/10.3390/jcm7090245
Received: 9 August 2018 / Revised: 23 August 2018 / Accepted: 24 August 2018 / Published: 28 August 2018
(This article belongs to the Section Molecular Medicine)
Adjuvant tamoxifen reduces the recurrence rate of estrogen receptor (ER)-positive breast cancer. Previous in vitro studies have suggested that tamoxifen can affect the cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein phosphatase 2A (PP2A)/phosphorylation Akt (pAkt) signaling in ER-negative breast cancer cells. In addition to CIP2A, SET nuclear proto-oncogene (SET) oncoprotein is another intrinsic inhibitor of PP2A, participating in cancer progression. In the current study, we explored the clinical significance of SET, CIP2A, PP2A, and Akt in patients with ER-positive breast cancer receiving adjuvant tamoxifen. A total of 218 primary breast cancer patients receiving adjuvant tamoxifen with a median follow-up of 106 months were analyzed, of which 17 (7.8%) experienced recurrence or metastasis. In an immunohistochemical (IHC) stain, SET overexpression was independently associated with worse recurrence-free survival (RFS) (hazard ratio = 3.72, 95% confidence interval 1.26–10.94, p = 0.017). In silico analysis revealed mRNA expressions of SET, PPP2CA, and AKT1 significantly correlated with worse RFS. In vitro, SET overexpression reduced tamoxifen-induced antitumor effects and drove luciferase activity in an Estrogen receptor element (ERE)-dependent manner. In conclusion, SET is a prognostic biomarker in patients with primary ER-positive breast cancer receiving adjuvant tamoxifen and may contribute to the failure of the tamoxifen treatment by modulating the ER signaling. Our study warrants further investigation into the potential role of SET in ER-positive breast cancer. View Full-Text
Keywords: breast cancer; tamoxifen; SET; CIP2A; PP2A breast cancer; tamoxifen; SET; CIP2A; PP2A
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Huang, Y.-H.; Chu, P.-Y.; Chen, J.-L.; Huang, C.-T.; Lee, C.-H.; Lau, K.-Y.; Wang, W.-L.; Wang, Y.-L.; Lien, P.-J.; Tseng, L.-M.; Liu, C.-Y. SET Overexpression is Associated with Worse Recurrence-Free Survival in Patients with Primary Breast Cancer Receiving Adjuvant Tamoxifen Treatment. J. Clin. Med. 2018, 7, 245.

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