Malignant MCF10CA1 cell lines derived from premalignant human breast epithelial MCF10AT cells

The MCF10 series of cell lines was derived from benign breast tissue from a woman with fibrocystic disease. The MCF10 human breast epithelial model sy stem consists of mortal MCF10M and MCF10MS (mortal cells grown in serum-fre e and serum-containing media, respectively), immortalized but otherwise nor mal MCF10F and MCF10A lines (free-floating versus growth as attached cells) , transformed MCF10AneoT cells transfected with T24 Ha-ras, and premalignan t MCF10AT cells with potential for neoplastic progression. The MCF10AT, der ived from xenograft-passaged MCF10-AneoT cells, generates carcinomas in sim ilar to 25% of xenografts. We now report the derivation of fully malignant MCF10CA1 lines that complete the spectrum of progression from relatively no rmal breast epithelial cells to breast cancer cells capable of metastasis. MCF10CA1 lines display histologic variations ranging from undifferentiated carcinomas, sometimes with focal squamous differentiation, to well-differen tiated adenocarcinomas. At least two metastasize to the lung following inje ction of cells into the tail vein; one line grows very rapidly in the lung, with animals moribund within 4 weeks, whereas the other requires 15 weeks to reach the same endpoint. In addition to variations in efficiency of tumo r production, the MCF10CA1 lines show differences in morphology in culture, anchorage-independent growth, karyotype, and immunocytochemistry profiles. The MCF10 model provides a unique tool for the investigation of molecular changes during progression of human breast neoplasia and the generation of tumor heterogeneity on a common genetic background.