Primed atypical ductal hyperplasia-associated fibroblasts promote cell growth and polarity changes of transformed epithelium-like breast cancer MCF-7 cells via miR-200b/c-IKKβ signaling.

Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating cancer cell proliferation, and invasion, but how the premalignant stromal fibroblasts trigger epithelial changes remain unclear. We demonstrate that atypical ductal hyperplasia-associated fibroblasts (AHFs) are one kind of activated fibroblasts and stimulate cell growth and polarity change of epithelium-like tumor cell MCF-7 as CAFs-like fibroblasts. Microarray shows miR-200b and miR-200c are downregulated during AHFs and CAFs, and contribute to stromal fibroblast activity. Additionally, miR-200b/c with target gene IKKβ (inhibitor of nuclear factor kappa-B kinase β) control PAI-1 (plasminogen activator inhibitor-1) expression to regulate growth and polarity changes of MCF-7 cells through NF-κB pathway. Exploring the difference of AHFs in premalignant transformation is crucial for understanding the pathobiology of breast cancer progression.