Abstract
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.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Basolo F., Elliott J., Tait L., Chen X. Q., Maloney T., Russo I. H., Pauley R., Momiki S., Caamano J., Klein-Szanto A. J. Transformation of human breast epithelial cells by c-Ha-ras oncogene. Mol Carcinog. 1991;4(1):25–35. doi: 10.1002/mc.2940040106. [DOI] [PubMed] [Google Scholar]
- Bos J. L. The ras gene family and human carcinogenesis. Mutat Res. 1988 May;195(3):255–271. doi: 10.1016/0165-1110(88)90004-8. [DOI] [PubMed] [Google Scholar]
- Garcia I., Dietrich P. Y., Aapro M., Vauthier G., Vadas L., Engel E. Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas. Cancer Res. 1989 Dec 1;49(23):6675–6679. [PubMed] [Google Scholar]
- Ma L., Boyd N. F. Atypical hyperplasia and breast cancer risk: a critique. Cancer Causes Control. 1992 Nov;3(6):517–525. doi: 10.1007/BF00052748. [DOI] [PubMed] [Google Scholar]
- Miller F. R., Soule H. D., Tait L., Pauley R. J., Wolman S. R., Dawson P. J., Heppner G. H. Xenograft model of progressive human proliferative breast disease. J Natl Cancer Inst. 1993 Nov 3;85(21):1725–1732. doi: 10.1093/jnci/85.21.1725. [DOI] [PubMed] [Google Scholar]
- Page D. L., Dupont W. D., Rogers L. W., Rados M. S. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer. 1985 Jun 1;55(11):2698–2708. doi: 10.1002/1097-0142(19850601)55:11<2698::aid-cncr2820551127>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
- Rochlitz C. F., Scott G. K., Dodson J. M., Liu E., Dollbaum C., Smith H. S., Benz C. C. Incidence of activating ras oncogene mutations associated with primary and metastatic human breast cancer. Cancer Res. 1989 Jan 15;49(2):357–360. [PubMed] [Google Scholar]
- Soule H. D., Maloney T. M., Wolman S. R., Peterson W. D., Jr, Brenz R., McGrath C. M., Russo J., Pauley R. J., Jones R. F., Brooks S. C. Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res. 1990 Sep 15;50(18):6075–6086. [PubMed] [Google Scholar]
- Tavassoli F. A., Norris H. J. A comparison of the results of long-term follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast. Cancer. 1990 Feb 1;65(3):518–529. doi: 10.1002/1097-0142(19900201)65:3<518::aid-cncr2820650324>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
- Theillet C., Lidereau R., Escot C., Hutzell P., Brunet M., Gest J., Schlom J., Callahan R. Loss of a c-H-ras-1 allele and aggressive human primary breast carcinomas. Cancer Res. 1986 Sep;46(9):4776–4781. [PubMed] [Google Scholar]
- Wolman S. R., Mohamed A. N., Heppner G. H., Soule H. D. Chromosomal markers of immortalization in human breast epithelium. Genes Chromosomes Cancer. 1994 May;10(1):59–65. doi: 10.1002/gcc.2870100110. [DOI] [PubMed] [Google Scholar]