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  • Title: Hypoxia promotes a dedifferentiated phenotype in ductal breast carcinoma in situ.
    Author: Helczynska K, Kronblad A, Jögi A, Nilsson E, Beckman S, Landberg G, Påhlman S.
    Journal: Cancer Res; 2003 Apr 01; 63(7):1441-4. PubMed ID: 12670886.
    Abstract:
    In cultured neuroblastoma cells, hypoxia induces a dedifferentiated phenotype. We tested whether hypoxia-induced dedifferentiation also occurs in vivo in mammary ductal carcinoma in situ with its well-defined lesions and distinct areas of necrosis. Ductal carcinoma in situ cells surrounding the central necrosis have high hypoxia inducible factor-1alpha protein levels, down-regulated estrogen receptor-alpha, and increased expression of the epithelial breast stem cell marker cytokeratin 19; lose their polarization; and acquire an increased nucleus/cytoplasm ratio, hallmarks of poor architectural and cellular differentiation. The hypoxia-induced changes were confirmed in cultured breast cancer cells. We propose that hypoxia-induced dedifferentiation is a mechanism that promotes tumor progression in breast cancer.
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