HLA-G and cancer: For example, HRE can be bound by hypoxia-inducible factor in response to hypoxia commonly observed in a majority of malignant tumors; an additional functional ISR that is located at position −746 is capable of transactivating HLA-G following administration of IFNs for immunotherapy of malignant diseases; PRE has been reported to mediate the up-regulation of HLA-G by progesterone implicated in breast cancer progression; HSE can bind heat shock factor 1 in response to hypoxic stress and induce HLA-G gene transcription.