The EU-funded project 'Analysis of the cellular origin of breast cancer' (BREAST CANCER ORIGIN) worked on identifying how breast cancer originates in cells. Researchers used the gene knockout technique (deleting key genes) in certain cell populations. Scientists used transgenic mouse models with inducible diphtheria toxin receptor (iDTR) as well as a slippage cassette having a dinucleotide repeat tract for their studies. Their purpose was to recreate human breast tumourigenesis conditions. However, further work is needed to optimise the slippage cassette for cancer studies. Project members were successful in deleting genes representing specific cell populations. Moreover, genes that can affect breast tissue structure and cell composition were also identified. Characterisation of genes led to the identification of a gene called regulator of mammary alveologenesis (Roma). This gene regulates the differentiation of cells into the milk-producing lineage. To study Roma gene function in mammary gland development, researchers generated a mouse model lacking the Roma gene. A novel finding is the possibility that Roma also regulates DNA damage response and could have tumour suppressive activity. Stat3 is a transcription factor that is activated in over 50 % of primary breast cancer cases and cancer cell lines. Studies revealed that mammary stem cells require Stat3 to maintain their ability to differentiate into different types of breast tissue. This suggests that Stat3 could also play a major role in activation of breast cancer stem cells. Project activities have identified novel factors that could play a key role in breast tumourigenesis. This has important implications when it comes to developing innovative and personalised therapies for breast cancer patients.
Breast cancer, genes, cell populations, transgenic mouse models, slippage cassette, tumourigenesis, Roma gene, Stat3, mammary stem cells