When there is a shortage of oxygen (hypoxia) in cells, the transcription factor hypoxia-inducible factor-1 (HIF-1) regulates processes that conserve cell energy and increase the energy supply to the cell. In breast cancer, the amount of HIF-1 alpha indicates the aggressiveness of the tumor and moreover predicts the patient’s life expectancy. In tissue, this transcription factor is found especially around areas with tissue death caused by hypoxia or diffused throughout the entire tumor.
Marije Vleugel’s research shows that nonhypoxia-inducible diffuse HIF-1 alpha is biologically less active than hypoxia-inducible HIF-1 alpha. This has emerged from differences in activation of certain genes and a prognosis that is relatively less poor for patients with diffuse HIF-1 alpha. These results point to a different way of regulating HIF-1 in breast cancer. Knowledge about this regulation mechanism is important for developing HIF-1-inhibiting anti-cancer therapies in future.
A number of different alternative regulation mechanisms have been described that could result in activating HIF-1 alpha at normal oxygen levels, such as HIF-1 gene mutations, activation of oncogenes, or mutations in tumor-suppressing genes. Vleugel was able to eliminate a number of these possibilities for diffuse HIF-1 alpha expression. Future research should focus on the cause of diffuse HIF-1 alpha expression and the absence of activation of HIF-1 target genes in breast cancer patients.
Marije Vleugel
HIF-1 alpha expression patterns in invasive breast cancer
PhD advisor 1: Prof. P.J. van Diest
PhD advisor 2: Prof. E. van der Wall
Co-advisor 1: Dr. A.E. Greijer
Co-advisor 2: Dr. R. Bos