Signalling mechanisms of lumen formation in breast cancer
2017
Beckman Research Institute of City of Hope, Duarte, USA
During cancer development, gene expression patterns change in cells undergoing transformation. In human breast tissue, there is a loss of lumenal expression of the CEACAM1 gene in the early stages of breast cancer. Some human breast cancer cell line cells regain the capacity of forming lumens when they are transfected with CEACAM1. Here, human breast cancer cells transfected with CEACAM1 are cultured in 3D and treated with a Jak2 inhibitor in order to elucidate the signalling mechanisms of the post-transfection gain of function. The results showed that lumen formation was hindered, probably driven by the inhibition of a set of genes downregulated in these cells. Furthermore, the selective downregulation of several of these genes blocked lumen formation. One of these genes, already described to be involved in mammary morphogenesis, was able to restore lumen formation when transfected in human breast cancer cells that lack CEACAM1 expression. Overall, the researchers suggest that lumenal formation involve several genes co-regulated with CEACAM1 and that modulation of some of these genes expression can recover some of the homeostatic functions of human breast cancer cells.
ETS transcription factor ELF5 induces lumen formation in a 3D model of mammary morphogenesis and its expression is inhibited by Jak2 inhibitor TG101348
John E Shively
Added on: 10-31-2021
[1] https://www.sciencedirect.com/science/article/abs/pii/S0014482717304196[2] https://data.jrc.ec.europa.eu/dataset/ffebe454-ed9a-47cf-8a33-8cf70c1b7d38
