hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.
hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.
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DOI：
10.1038/bjc.2015.28
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发表时间：
2015-03-17
影响因子：
8.8
通讯作者：
Arcangeli, A.
中科院分区：
文献类型：
--
作者：
Lastraioli, E.;Perrone, G.;Sette, A.;Fiore, A.;Crociani, O.;Manoli, S.;D'Amico, M.;Masselli, M.;Iorio, J.;Callea, M.;Borzomati, D.;Nappo, G.;Bartolozzi, F.;Santini, D.;Bencini, L.;Farsi, M.;Boni, L.;Di Costanzo, F.;Schwab, A.;Muda, A. Onetti;Coppola, R.;Arcangeli, A.
HERG1通道在人类肿瘤中异常表达。目前尚缺乏HERG1通道在胰腺导管腺癌中的表达、功能及临床意义。用抗hERG1McAb(α-hERG1Moab)免疫组织化学方法检测hERG1DNA在组织芯片中的表达。研究hERG1在PDAC细胞株和原代培养中的功能作用。研究了PDX-1-CRE、LSL-KrasG12D/+、LSL-Trp53R175H/+转基因(KPC)小鼠PDAC进展过程中ERG1的表达。用ALEXA-680标记的α-hERG1-Moab进行光学成像，检测ERG1在体内的表达。(I)hERG1在59%的原代PDAC中高表达；(Ii)hERG1阻断pDAC细胞的生长和迁移；(Iii)hERG1在物理和功能上与表皮生长因子受体途径有关；(Iv)在转基因小鼠中，hERG1在PAN中表达，并在pDAC中高表达；(V)原发肿瘤hERG1高表达的pDAC患者预后较差；(Vi)α-hERG1-Moab可在体内检测到pDAC。HERG1调节PDAC的恶性程度，其表达一旦在包括晚期、非手术切除病例在内的更大的队列中得到证实，则可能被用于体外或体内的PDAC的诊断和预后目的。
hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-KrasG12D/+,LSL-Trp53R175H/+ transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.
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影响因子：
5
作者：
Lastraioli, Elena;Bencini, Lapo;Arcangeli, Annarosa
通讯作者：
Arcangeli, Annarosa
影响因子：
2.9
作者：
Deer EL;González-Hernández J;Coursen JD;Shea JE;Ngatia J;Scaife CL;Firpo MA;Mulvihill SJ
通讯作者：
Mulvihill SJ
影响因子：
--
作者：
Neuzillet C;de Gramont A;Tijeras-Raballand A;de Mestier L;Cros J;Faivre S;Raymond E
通讯作者：
Raymond E
影响因子：
3.6
作者：
Gasparoli, Luca;D'Amico, Massimo;Arcangeli, Annarosa
通讯作者：
Arcangeli, Annarosa
影响因子：
5.6
作者：
Lastraioli, Elena;Taddei, Antonio;Arcangeli, Annarosa
通讯作者：
Arcangeli, Annarosa