Technical challenges and limitations of current mouse models of ovarian cancer.
Technical challenges and limitations of current mouse models of ovarian cancer.
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DOI：
10.1186/1757-2215-5-39
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发表时间：
2012-11-29
影响因子：
4
通讯作者：
Vanderhyden BC
中科院分区：
文献类型：
--
作者：
Garson K;Gamwell LF;Pitre EM;Vanderhyden BC
上皮性卵巢癌（EOC）的基因工程模型（GEM）的开发已经非常成功，具有代表高级别和低级别浆液性腺癌和类浆液性癌（EC）的充分验证的模型。这些模型中的大多数是使用旨在靶向卵巢表面上皮（OSE）的技术开发的，该细胞类型长期被认为是EOC的起源。最近的证据强调了输卵管分泌细胞在EOC个体发生中可能更普遍的作用，然而EOC的GEM都没有成功靶向这种重要的细胞类型。用于开发EOC现有GEM的精确技术多种多样，并且具有优点和缺点。使用组织特异性启动子来模拟疾病已经非常成功，但是缺乏任何真正特异性的OSE或输卵管分泌细胞启动子使得这些模型的结果非常不可预测。通过施用表达Cre重组酶的腺病毒载体来实现遗传变化可以减轻对组织特异性启动子的感知需求，然而，不同细胞类型的感染效率受到许多生物学参数的影响，这些生物学参数可能导致某些细胞群体的优先靶向。EOC GEM的一个重要的未来途径是评估遗传修饰剂的作用。我们已经发现，遗传背景可以导致卵巢癌的一个模型中的对比表型，来自其他实验室的数据也暗示，模型的确切遗传背景可能会影响所得的表型。不同的遗传背景可能以与人类疾病相关的方式改变肿瘤的生物学，但它们也可能改变影响宿主对开发模型所采用的技术的反应的参数。
The development of genetically engineered models (GEM) of epithelial ovarian cancer (EOC) has been very successful, with well validated models representing high grade and low grade serous adenocarcinomas and endometrioid carcinoma (EC). Most of these models were developed using technologies intended to target the ovarian surface epithelium (OSE), the cell type long believed to be the origin of EOC. More recent evidence has highlighted what is likely a more prevalent role of the secretory cell of the fallopian tube in the ontogeny of EOC, however none of the GEM of EOC have demonstrated successful targeting of this important cell type. The precise technologies exploited to develop the existing GEM of EOC are varied and carry with them advantages and disadvantages. The use of tissue specific promoters to model disease has been very successful, but the lack of any truly specific OSE or oviductal secretory cell promoters makes the outcomes of these models quite unpredictable. Effecting genetic change by the administration of adenoviral vectors expressing Cre recombinase may alleviate the perceived need for tissue specific promoters, however the efficiencies of infection of different cell types is subject to numerous biological parameters that may lead to preferential targeting of certain cell populations. One important future avenue of GEM of EOC is the evaluation of the role of genetic modifiers. We have found that genetic background can lead to contrasting phenotypes in one model of ovarian cancer, and data from other laboratories have also hinted that the exact genetic background of the model may influence the resulting phenotype. The different genetic backgrounds may modify the biology of the tumors in a manner that will be relevant to human disease, but they may also be modifying parameters which impact the response of the host to the technologies employed to develop the model.
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影响因子：
9.2
作者：
Chodankar, R;Kwang, S;Dubeau, L
通讯作者：
Dubeau, L
影响因子：
3.7
作者：
Clark-Knowles KV;Senterman MK;Collins O;Vanderhyden BC
通讯作者：
Vanderhyden BC
影响因子：
82.9
作者：
Dinulescu, DM;Ince, TA;Jacks, T
通讯作者：
Jacks, T
DOI：
10.1097/01.pgp.0000101082.35393.84
发表时间：
2004-01-01
影响因子：
2.4
作者：
Carcangiu, ML;Radice, P;Pasini, B
通讯作者：
Pasini, B
影响因子：
4.8
作者：
Arici, A;Oral, E;Olive, DL
通讯作者：
Olive, DL