Results of transgenic mouse study directly applicable to human breast cancer tumor study
Sanford Barsky, M.D., who holds faculty positions at the University of Nevada School of Medicine as chair of the pathology department and Nevada Cancer Institute chief of pathology, is part of a team that has a paper on transgenic mouse mammary tumors with direct relevance to human breast cancer published in the October 22 issue of the scientific journal Nature.
The article, "Pten in stromal fibroblasts suppresses mammary epithelial tumours," shows that a key signaling pathway that operates in mammary gland connective tissue cells helps to suppress the development of mammary tumors. This study is important because it helps tease apart the complex links between tumor microenvironment and cancer development.
It had been thought that the connective tissue surrounding tumors - also known as the tumor microenvironment - is important for helping the tumor to grow and survive, but it was not clear just how. This study revealed that deletion of the tumour suppressor gene Pten in fibroblasts - connective tissue cells - of mammary glands leads to the accelerated development of mammary tumors in mice. Furthermore, tumor development goes hand-in-hand with other changes in the local cellular environment, such as increased blood vessel formation and immune cell infiltration.
Pten loss and related changes in gene expression can also be observed in the connective tissue of breast cancers in women, suggesting that the signalling system operates in humans as well as mice. The team also highlights Pten's influence on a transcription factor called Ets2 as being critical for Pten's tumour suppressive functions in the connective tissue.