CITED2 in breast carcinoma as a potent prognostic predictor associated with proliferation, migration and chemoresistance.
CITED2 in breast carcinoma as a potent prognostic predictor associated with proliferation, migration and chemoresistance.
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DOI：
10.1111/cas.13081
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发表时间：
2016-12
期刊：
影响因子：
5.7
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Minemura H;Takagi K;Sato A;Takahashi H;Miki Y;Shibahara Y;Watanabe M;Ishida T;Sasano H;Suzuki T
CITED 2（Cbp/p300相互作用反式激活因子，具有富含Glu/Asp的羧基末端结构域，2）是CITED家族的成员，参与发育和分化过程中的各种细胞功能。越来越多的证据表明CITED在人类恶性肿瘤进展中的重要性，但CITED 2蛋白在乳腺癌中的意义尚未得到研究。因此，本研究通过免疫组化和体外研究，探讨CITED 2在乳腺癌中的临床意义和生物学功能。CITED 2在乳腺癌组织中的表达明显高于正常乳腺组织。CITED 2免疫反应性与分期、病理T因子、淋巴结转移、组织学分级、HER 2和Ki-67显著相关，与雌激素受体呈负相关。此外，免疫组化CITED 2状态与乳腺癌患者复发和乳腺癌特异性死亡的发生率增加显著相关，多变量分析表明CITED 2状态是无病生存和乳腺癌特异性生存的独立不良预后因素。随后的体外实验表明，CITED 2表达显著增加了MCF-7和S KBR-3乳腺癌细胞的增殖活性和迁移特性。此外，CITED 2在这些细胞中引起对表阿霉素和5-氟尿嘧啶的化学抗性，但不是紫杉醇，并且它在5-氟尿嘧啶处理后抑制MCF-7细胞中p53的积累。这些结果表明CITED 2在乳腺癌的进展和化疗耐药性中起重要作用，CITED 2状态是乳腺癌患者的有效预后因素。
CITED2 (Cbp/p300‐interacting transactivator, with Glu/Asp‐rich carboxy‐terminal domain, 2) is a member of the CITED family and is involved in various cellular functions during development and differentiation. Mounting evidence suggests the importance of CITED in the progression of human malignancies, but the significance of CITED2 protein has not yet been examined in breast carcinoma. Therefore, in the present study, we examined the clinical significance and the biological functions of CITED2 in breast carcinoma by immunohistochemistry and in vitro study. CITED2 immunoreactivity was detected in breast carcinoma tissues, and it was significantly higher compared to those in morphologically normal mammary glands. CITED2 immunoreactivity was significantly associated with stage, pathological T factor, lymph node metastasis, histological grade, HER2 and Ki‐67, and inversely correlated with estrogen receptor. Moreover, the immunohistochemical CITED2 status was significantly associated with increased incidence of recurrence and breast cancer‐specific death of the breast cancer patients, and multivariate analyses demonstrated CITED2 status as an independent worse prognostic factor for disease‐free and breast cancer‐specific survival. Subsequent in vitro experiments showed that CITED2 expression significantly increased proliferation activity and migration property in MCF‐7and S KBR‐3 breast carcinoma cells. Moreover, CITED2 caused chemoresistance to epirubicin and 5‐fluorouracil, but not paclitaxel, in these cells, and it inhibited p53 accumulation after 5‐fluorouracil treatment in MCF‐7 cells. These results suggest that CITED2 plays important roles in the progression and chemoresistance of breast carcinoma and that CITED2 status is a potent prognostic factor in breast cancer patients.
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影响因子：
9
作者：
Haupt S;Buckley D;Pang JM;Panimaya J;Paul PJ;Gamell C;Takano EA;Lee YY;Hiddingh S;Rogers TM;Teunisse AF;Herold MJ;Marine JC;Fox SB;Jochemsen A;Haupt Y
通讯作者：
Haupt Y
影响因子：
3.5
作者：
Budman, DR;Calabro, A
通讯作者：
Calabro, A
影响因子：
8
作者：
McBryan, J.;Howlin, J.;Martin, F.
通讯作者：
Martin, F.
影响因子：
8
作者：
Chou, Y-T;Wang, H.;Yang, Y-C
通讯作者：
Yang, Y-C
影响因子：
11.2
作者：
Fox, SB;Bragança, J;Harris, AL
通讯作者：
Harris, AL