MCF10AT: a model for the evolution of cancer from proliferative breast disease.
MCF10AT: a model for the evolution of cancer from proliferative breast disease.
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发表时间：
1996
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通讯作者：
P. Dawson;S. Wolman;L. Tait;G. Heppner;F. Miller
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作者：
P. Dawson;S. Wolman;L. Tait;G. Heppner;F. Miller
一个人类细胞系（MCF10A）起源于从纤维囊性疾病患者获得的乳腺上皮细胞的自发永生。MCF10A细胞在免疫缺陷小鼠体内不能存活。然而，T24 c-Ha-ras癌基因转染的MCF10A细胞（MCF10AT）在裸/米色小鼠中形成小结节，持续至少1年，偶尔进展为癌。通过在组织培养中重建来自其中一种癌的细胞，获得了一种命名为MCF10AT1的细胞系，当将其在Matrigel中移植到免疫缺陷小鼠中时，该细胞系形成了简单的导管。随着时间的推移，上皮细胞开始增殖，异种移植物内形成筛网状。在女性中，相当一部分发展为类似于非典型增生和原位癌的病变，大约25%发展为浸润性癌，具有各种类型的分化，包括腺癌、鳞状癌和未分化癌。细胞已经从代表连续移植代的病变中建立。每一代细胞都更有可能发展成类似人类乳腺增生性疾病的高风险病变。虽然浸润性癌的发病率保持在20% - 25%的相当稳定，但显示增生性乳腺疾病的结节的频率从第一代移植的23%上升到第四代移植的56%。
A human cell line (MCF10A) originated from spontaneous immortalization of breast epithelial cells obtained from a patient with fibrocystic disease. MCF10A cells do not survive in vivo in immunodeficient mice. However, T24 c-Ha-ras oncogene-transfected MCF10A cells (MCF10AT) form small nodules in nude/beige mice that persist for at least 1 year and sporadically progress to carcinomas. By reestablishing cells in tissue culture from one of the carcinomas, a cell line designated MCF10AT1 was derived that forms simple ducts when transplanted in Matrigel into immunodeficient mice. With time in vivo, the epithelium becomes proliferative and a cribriform pattern develops within the xenografts. A significant number progress to lesions resembling atypical hyperplasia and carcinoma in situ in women, and approximately 25% progress to invasive carcinomas with various types of differentiation including glandular, squamous, and undifferentiated. Cells have been established in culture from lesions representing successive transplant generations. With each generation, cells are somewhat more likely to progress to high risk lesions resembling human proliferative breast disease. Although the incidence of invasive carcinoma remained fairly constant at 20 to 25%, the frequency of nodules showing proliferative breast disease rose from 23% in the first transplant generation to 56% in the fourth transplant generation.