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Hypoxia Promotes a Dedifferentiated Phenotype in Ductal Breast Carcinoma in Situ1

Hypoxia Promotes a Dedifferentiated Phenotype in Ductal Breast Carcinoma in Situ1,Karolina Helczynska,Åsa Kronblad,Annika Jogi,Elise Nilsson,Siv Beckm

Hypoxia Promotes a Dedifferentiated Phenotype in Ductal Breast Carcinoma in Situ1   (Citations: 28)
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In cultured neuroblastoma cells, hypoxia induces a dedifferentiated phenotype. We tested whether hypoxia-induced dedifferentiation also oc- curs 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-1 protein levels, down-regulated estrogen receptor-, and increased expres- sion 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.
Published in 2003.
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    • ...Hypoxia is commonly found in solid tumors and is able to profoundly alter the expression of a wide range of genes, leading to a dedifferentiated, more aggressive phenotype as well as therapy resistance (15, 16)...
    • ...Moreover, it has been shown that hypoxia leads to a dedifferentiated phenotype in ductal carcinoma in situ and in breast cancer cell lines (16), a finding that is in line with the reduction of C/EBPa expression shown in the present study...

    Ramzi Seifeddineet al. Hypoxia Down-regulates CCAAT/Enhancer Binding Protein-A Expression in ...

    • ...Interestingly, as lymphoma cells are known to express various degrees of CD31 (59) and hypoxia can regulate differentiation of malignant cells (23, 29), the possibility exists that LCLs could switch to an endothelial cell phenotype in vivo under conditions where angiogenesis is needed...

    Gregory K. Honget al. Epstein-Barr Virus Lytic Infection Is Required for Efficient Productio...

    • ...For example, transcription of genes regulating angiogenesis, metabolism, and survival is altered, resulting in a more resilient phenotype (1, 2). In malignant tumors, this phenotype has previously been assigned immature, stem cell–like properties (3, 4). As tumor hypoxia is generally linked to poor prognosis (5–7), we proposed that hypoxia-driven dedifferentiation is one factor behind the development of a more aggressive phenotype (8)...

    Karolina Helczynskaet al. Hypoxia-Inducible Factor2A Correlates to Distant Recurrence and Poor O...

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