A transgenic mouse model for the ductal carcinoma in situ (DCIS) of the mammary gland
A transgenic mouse model for the ductal carcinoma in situ (DCIS) of the mammary gland
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DOI：
10.1038/sj.onc.1203281
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发表时间：
2000-02-21
期刊：
影响因子：
8
通讯作者：
Deppert, W
中科院分区：
文献类型：
--
作者：
Schulze-Garg, C;Löhler, J;Deppert, W
乳腺导管原位癌（DCIS）代表了浸润性乳腺癌发展的早期、侵袭前阶段，随着高质量乳房x线摄影筛查的引入，越来越多的人被诊断出来。DCIS患者预后的不确定性引起了关于适当治疗的争议，并且怀疑大多数接受乳房切除术的患者可能被过度治疗，因此确定DCIS的预后标志物和治疗靶点是非常必要的，以改善治疗和治疗决策。我们在此介绍了一组转基因小鼠（WAP-T和WAP-T- np系），它们表现出不同形态的dcls样病变。在这些螨中，SV40大肿瘤抗原在末端导管小叶单位（TDLU）的上皮细胞中被特异性诱导，作为癌基因持续表达的结果，动物在菌株特定的潜伏期内发展为多灶性DCIS，从而发展为侵袭性癌。转基因泥水中的DCIS病变表现出与人类非常相似的独特结构和细胞学特征，因此我们提出这些转基因系作为实验模型来研究导致DCIS及其进展为侵袭性疾病的潜在分子事件。
The ductal carcinoma in situ (DCIS) of the mammary gland represents an early, pre-invasive stage in the development of invasive breast carcinoma and is increasingly diagnosed since the introduction of high-quality mammography screening. Uncertainties in the prognosis for patients with DCIS have caused a controversial discussion about adequate treatment, and it is suspected that most patients undergoing mastectomy may be overtreated, In order to improve treatment and treatment decision, it therefore is highly desirable to identify prognostic markers and therapeutic targets for DCIS. We here introduce a set of transgenic mice (WAP-T and WAP-T-NP lines) presenting with various morphological forms of DCLS-like lesions. In these mite the SV40 large tumor antigen is specifically induced in epithelial cells of the terminal duct lobular units (TDLU), As a consequence of continuous expression of the oncogene, the animals develop multifocal DCIS and consequently invasive carcinoma within strain specific periods of latency. DCIS lesions in transgenic mire exhibit distinct architectural and cytological features which closely resemble those commonly present in humans, We therefore propose these transgenic lines as an experimental model to study the underlying molecular events leading to DCIS and its progression to invasive disease.