Antiestrogen-resistant subclones of MCF-7 human breast cancer cells are derived from a common monoclonal drug-resistant progenitor

摘要: Emergence of antiestrogen-resistant cells in MCF-7 during suppression estrogen signaling is a widely accepted model acquired breast cancer resistance to endocrine therapy. To obtain insight into the genomic basis therapy resistance, we characterized monoclonal sublines that survived 21-day exposure tamoxifen (T-series sublines) or fulvestrant (F-series and unselected by drugs (U-series). All T/F-sublines were resistant cytocidal effects both fulvestrant. However, their responses cytostatic varied greatly, remarkably diversified morphology showed no correlation with drug resistance. mRNA expression profiles U-sublines differed significantly from those T/F-sublines, whose transcriptomal responsiveness was largely lost. A set genes strongly expressed successfully predicted metastasis-free survival patients. Most shared highly homogeneous DNA aberration patterns distinct U-sublines. Genomic harbored many aberrations not found T/F-sublines. These results suggest are derived common progenitor lost antiestrogens as consequence genetic abnormalities population doublings ago, antiestrogen-sensitive same culture antiestrogens. Thus, apparent acquisition antiestrogen reflects selection preexisting drug-resistant subpopulations without involving changes individual cells. Our importance clonal cancer.