Pathologic progression of mammary carcinomas in a C3(1)/SV40 T/t-antigen transgenic rat model of human triple-negative and Her2-positive breast cancer.
Pathologic progression of mammary carcinomas in a C3(1)/SV40 T/t-antigen transgenic rat model of human triple-negative and Her2-positive breast cancer.
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DOI：
10.1007/s11248-010-9406-5
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发表时间：
2011-04
影响因子：
3
通讯作者：
Green JE
中科院分区：
文献类型：
--
作者：
Hoenerhoff MJ;Shibata MA;Bode A;Green JE
大鼠前列腺类固醇结合蛋白的C3（1）组分已被用于靶向表达SV 40 T/t-抗原至小鼠乳腺上皮，导致肿瘤前病变进展为具有人基底型乳腺癌分子特征的浸润性和转移性癌症。然而，小鼠和人乳腺间质和上皮成分的组织学结构存在重大差异。大鼠乳腺比小鼠乳腺更富含上皮和基质成分，并且更接近于人类乳腺的细胞组成。此外，现有的乳腺癌大鼠模型通常是雌激素受体阳性和激素反应性的，不像大多数基因工程小鼠乳腺癌模型。为了开发一种可能更接近人类乳腺癌病理学的乳腺癌模型，我们建立了一种新型C3（1）/SV 40 T/t抗原转基因大鼠模型，该模型发生了导致高度浸润性腺癌的进行性乳腺病变。然而，侵袭性肿瘤的发展阻止了转基因系的建立。肿瘤的特征显示，它们主要是雌激素受体和孕激素受体阴性，以及her 2/neu阳性或阴性，类似于人类三阴性或Her 2阳性乳腺癌。肿瘤表达基础标记物K14以及管腔标记物K18，并且对平滑肌肌动蛋白呈阴性。在大鼠乳腺癌模型中尚未报道三阴性表型。进一步开发基于C3（1）SV 40 T/t抗原的模型可以建立有价值的转基因大鼠系，这些大鼠系发生基底型乳腺肿瘤。
The C3(1) component of the rat prostate steroid binding protein has been used to target expression of the SV40 T/t-antigen to the mammary epithelium of mice resulting in pre-neoplastic lesions that progress to invasive and metastatic cancer with molecular features of human basal-type breast cancer. However, there are major differences in the histologic architecture of the stromal and epithelial elements between the mouse and human mammary glands. The rat mammary gland is more enriched with epithelial and stromal components than the mouse and more closely resembles the cellular composition of the human gland. Additionally, existing rat models of mammary cancer are typically estrogen receptor positive and hormone responsive, unlike most genetically engineered mouse mammary cancer models. In an attempt to develop a mammary cancer model that might more closely resemble the pathology of human breast cancer, we generated a novel C3(1)/SV40 T/t-antigen transgenic rat model that developed progressive mammary lesions leading to highly invasive adenocarcinomas. However, aggressive tumor development prevented the establishment of transgenic lines. Characterization of the tumors revealed that they were primarily estrogen receptor and progesterone receptor negative, and either her2/neu positive or negative, resembling human triple-negative or Her2 positive breast cancer. Tumors expressed the basal marker K14, as well as the luminal marker K18, and were negative for smooth muscle actin. The triple negative phenotype has not been previously reported in a rat mammary cancer model. Further development of a C3(1)SV40 T/t-antigen based model could establish valuable transgenic rat lines that develop basal-type mammary tumors.
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影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
11.2
作者：
Deeb, Kristin K.;Michalowska, Aleksandra M.;Green, Jeffrey E.
通讯作者：
Green, Jeffrey E.
影响因子：
8
作者：
Doane, A. S.;Danso, M.;Gerald, W. L.
通讯作者：
Gerald, W. L.
影响因子：
7.5
作者：
Livasy, CA;Karaca, G;Perou, CM
通讯作者：
Perou, CM
基础细胞角蛋白及其与乳腺癌的细胞起源和功能分类的关系。
影响因子：
7.4
作者：
Gusterson, BA;Ross, DT;Heath, VJ;Stein, T
通讯作者：
Stein, T