SET Overexpression is Associated with Worse Recurrence-Free Survival in Patients with Primary Breast Cancer Receiving Adjuvant Tamoxifen Treatment.
SET Overexpression is Associated with Worse Recurrence-Free Survival in Patients with Primary Breast Cancer Receiving Adjuvant Tamoxifen Treatment.
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固定过表达与接受他莫昔芬辅助治疗的原发性乳腺癌患者的无复发生存率较差有关。
DOI：
10.3390/jcm7090245
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发表时间：
2018-08-28
影响因子：
3.9
通讯作者：
Liu CY
中科院分区：
文献类型：
--
作者：
Huang YH;Chu PY;Chen JL;Huang CT;Lee CH;Lau KY;Wang WL;Wang YL;Lien PJ;Tseng LM;Liu CY
辅助性他莫昔芬可降低雌激素受体（ER）阳性乳腺癌的复发率。以前的体外研究表明，他莫昔芬可以影响ER阴性乳腺癌细胞中蛋白磷酸酶2A（CIP 2A）/蛋白磷酸酶2A（PP 2A）/磷酸化Akt（pAkt）信号传导的癌性抑制剂。除了CIP 2A之外，SET核原癌基因（SET）癌蛋白是PP 2A的另一种内在抑制剂，参与癌症进展。在本研究中，我们探讨了SET、CIP 2A、PP 2A和Akt在接受他莫昔芬辅助治疗的ER阳性乳腺癌患者中的临床意义。共分析了218例接受他莫昔芬辅助治疗的原发性乳腺癌患者，中位随访时间为106个月，其中17例（7.8%）复发或转移。在免疫组化（IHC）染色中，SET过表达与更差的无复发生存率（RFS）独立相关（风险比= 3.72，95%置信区间1.26-10.94，p = 0.017）。计算机模拟分析显示SET、PPP 2CA和AKT 1的mRNA表达与RFS恶化显著相关。在体外，SET过表达降低了他莫昔芬诱导的抗肿瘤作用，并以雌激素受体元件（ERE）依赖的方式驱动荧光素酶活性。总之，SET是接受他莫昔芬辅助治疗的原发性ER阳性乳腺癌患者的预后生物标志物，并可能通过调节ER信号传导导致他莫昔芬治疗失败。我们的研究需要进一步研究SET在ER阳性乳腺癌中的潜在作用。
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.
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影响因子：
168.9
作者：
Davies, Christina;Pan, Hongchao;Godwin, Jon;Gray, Richard;Arriagada, Rodrigo;Raina, Vinod;Abraham, Mirta;Medeiros Alencar, Victor Hugo;Badran, Atef;Bonfill, Xavier;Bradbury, Joan;Clarke, Michael;Collins, Rory;Davis, Susan R.;Delmestri, Antonella;Forbes, John F.;Haddad, Peiman;Hou, Ming-Feng;Inbar, Moshe;Khaled, Hussein;Kielanowska, Joanna;Kwan, Wing-Hong;Mathew, Beela S.;Mittra, Indraneel;Mueller, Bettina;Nicolucci, Antonio;Peralta, Octavio;Pernas, Fany;Petruzelka, Lubos;Pienkowski, Tadeusz;Radhika, Ramachandran;Rajan, Balakrishnan;Rubach, Maryna T.;Tort, Sera;Urrutia, Gerard;Valentini, Miriam;Wang, Yaochen;Peto, Richard
通讯作者：
Peto, Richard
PP2A抑制剂SET癌蛋白的过度表达与人类非小细胞肺癌的肿瘤进展和不良预后相关
影响因子：
--
作者：
Liu H;Gu Y;Wang H;Yin J;Zheng G;Zhang Z;Lu M;Wang C;He Z
通讯作者：
He Z
DOI：
10.1186/bcr2890
发表时间：
2011-06-27
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Colombo PE;Milanezi F;Weigelt B;Reis-Filho JS
通讯作者：
Reis-Filho JS
影响因子：
50.3
作者：
Neviani, P;Santhanam, R;Perrotti, D
通讯作者：
Perrotti, D
影响因子：
4.8
作者：
Hall, JM;McDonnell, DP
通讯作者：
McDonnell, DP