The effect of hypoxia on the differentiation state in triple negative breast cancer

Breast cancer is the major leading cause of death in women and is considered to be malignant, invasive and metastatic.Recently, the understanding of the disease and its underlying mechanisms has significantly improved, leading to novel treatments for some forms of breast cancer. However, certain subtypes still have poor prognosis.
Most breast cancers express estrogen receptor (ER), progesterone receptor (PR) and HER2. Inhibition of these genes is used as a therapeutic approach to cure breast cancer. However, triple negative breast cancer (TNBC) lacks expression of these three genes. Therefore, it is considered an aggressive cancer.
Hypoxia is a hallmark of cancer that contributes to metastasis, treatment failure and patient mortality. It is mediated by hypoxia inducible factor, HIF1A.Lack of O₂ causes stabilization and activation of the HIF1A protein and its downstream targets. It has been shown that hypoxia results in deregulation of genes related to EMT and Notch pathway. The aim of our study is to understand the role of hypoxia in TNBC and determine its mechanism. Towards this aim, we cultured the TNBC cell line, HCC70, in a hypoxia chamber containing 1% O₂ for 7 days. We observed downregulation of genes associated with luminal progenitor, mature luminal and basal cell population differentiation gene signatures. We plan to use hypoxia and notch reporters in TNBC cell lines to elucidate the functional interaction between notch signaling and hypoxia, and to establish the impact on the differentiation state. We believe that this research will contribute to a better understanding of TNBC, perhaps leading to novel therapeutic targets.