Biologic roles of estrogen receptor-β and insulin-like growth factor-2 in triple-negative breast cancer.
Biologic roles of estrogen receptor-β and insulin-like growth factor-2 in triple-negative breast cancer.
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DOI：
10.1155/2015/925703
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发表时间：
2015
影响因子：
--
通讯作者：
Pietras R
中科院分区：
文献类型：
--
作者：
Hamilton N;Márquez-Garbán D;Mah V;Fernando G;Elshimali Y;Garbán H;Elashoff D;Vadgama J;Goodglick L;Pietras R
三阴性乳腺癌(TNBC)发生在10%-15%的患者中，但几乎占所有乳腺癌死亡人数的一半。TNBCs缺乏雌激素和孕激素受体的表达以及HER-2的过度表达，无法用目前的靶向治疗。TNBC通常发生在非裔美国人和年轻女性中。虽然最初对一些化疗药物有反应，但TNBCs往往会复发和转移。因此，寻找新的治疗靶点至关重要。第二个ER基因产物，称为ERβ，在缺乏ERα的情况下可能是这样的靶点。使用已知临床结果的人TNBC标本评估ERβ的表达，我们发现ERβ1与显著较差的5年总生存率相关。此外，一组TNBC细胞系显示出显著的ERβ蛋白水平。为了评估ERβ对细胞增殖的影响，利用shRNA沉默了肿瘤细胞中ERβ的表达，从而显著抑制了肿瘤细胞的增殖。ERβ特异性拮抗剂同样抑制肿瘤细胞的生长。ERβ的生长刺激作用可能部分归因于促进血管内皮生长因子、两端调节素和WNT-10b分泌的下游作用，以及其他与肿瘤促进相关的因子。在体内，胰岛素样生长因子-2(IGF2)和ERβ1在TNBC中显著表达，并刺激TNBC细胞中高ERβ的表达。这项工作可能有助于阐明代谢和生长因子在TNBC中的相互作用。
Triple-negative breast cancer (TNBC) occurs in 10–15% of patients yet accounts for almost half of all breast cancer deaths. TNBCs lack expression of estrogen and progesterone receptors and HER-2 overexpression and cannot be treated with current targeted therapies. TNBCs often occur in African American and younger women. Although initially responsive to some chemotherapies, TNBCs tend to relapse and metastasize. Thus, it is critical to find new therapeutic targets. A second ER gene product, termed ERβ, in the absence of ERα may be such a target. Using human TNBC specimens with known clinical outcomes to assess ERβ expression, we find that ERβ1 associates with significantly worse 5-year overall survival. Further, a panel of TNBC cell lines exhibit significant levels of ERβ protein. To assess ERβ effects on proliferation, ERβ expression in TNBC cells was silenced using shRNA, resulting in a significant reduction in TNBC proliferation. ERβ-specific antagonists similarly suppressed TNBC growth. Growth-stimulating effects of ERβ may be due in part to downstream actions that promote VEGF, amphiregulin, and Wnt-10b secretion, other factors associated with tumor promotion. In vivo, insulin-like growth factor-2 (IGF-2), along with ERβ1, is significantly expressed in TNBC and stimulates high ERβ mRNA in TNBC cells. This work may help elucidate the interplay of metabolic and growth factors in TNBC.
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影响因子：
7.4
作者：
Bilir B;Kucuk O;Moreno CS
通讯作者：
Moreno CS
影响因子：
50.5
作者：
Corkery, B.;Crown, J.;O'Donovan, N.
通讯作者：
O'Donovan, N.
影响因子：
10.3
作者：
JIANG, SY;JORDAN, VC
通讯作者：
JORDAN, VC
影响因子：
9.7
作者：
JENG, MH;JIANG, SY;JORDAN, VC
通讯作者：
JORDAN, VC
DOI：
10.1016/j.jsbmb.2009.05.004
发表时间：
2009-08
影响因子：
4.1
作者：
Hershberger, Pamela A.;Stabile, Laura P.;Kanterewicz, Beatriz;Rothstein, Mary E.;Gubish, Chris T.;Land, Stephanie;Shuai, Yongli;Siegfried, Jill M.;Nichols, Mark
通讯作者：
Nichols, Mark