Functional analysis of normal and DCIS modified breast myoepithelial cells

Normal breast myoepithelial cells have been shown to exhibit tumour-suppressor activity mediated, in part, by downregulation of MMP expression [1]. DCIS myoepithelial cells have an altered phenotype as demonstrated by a different gene expression profile [2]. We have identified upregulation of α(v)β₆ integrin on myoepithelial cells in a subset of DCIS; however, the role of α(v)β₆ in this context is not clear. α(v)β₆ is not expressed by normal epithelial cells, but is expressed in some cancers where it promotes tumour cell invasion and enhances MMP expression.

The purpose of this project is to investigate the hypothesis that DCIS-associated myoepithelial cells lose their tumour suppressor effect and acquire a tumour promoting activity. There are three general aims: (1) to generate a series of myoepithelial cell models to mimic DCIS-associated myoepithelial cells and overexpress α(v)β₆ to assess the contribution of this integrin; (2) to compare tumour suppressor/promoter properties of normal, α(v)β₆ overexpressing and DCIS-associated myoepithelial cells; and (3) to examine the effect of de novo α(v)β₆ expression on the biological activity of myoepithelial cells.

We have fully characterised an immortalised myoepithelial cell line, engineered it to overexpress α(v)β₆ and determined that it is functional. We are starting to examine the morphology and phenotype of these cells to determine any differences, and we have been able to show the parental cell line is able to recapitulate the tumour suppressor effect in in vitro systems. We are now looking into what effect the expression of α(v)β₆ has in these systems. We are also in the process of trying to create further myoepithelial cell lines from primary cells isolated from patient tissue.

Through this work we hope to identify the role α(v)β₆ expression has in DCIS myoepithelial cells with the goal of making this integrin a viable therapeutic target in the future.