Altered myoepithelial cell expression and function in cancer-containing breasts

We have previously identified that the noninvolved tissue from breasts that contains a cancer (NTCCB) differs from age-matched normal breast from women without cancer, having lower apoptotic indices [1] and altered expression of epidermal growth factor receptor [2] and β₄ integrin [3]. Both of the latter are proteins expressed by myoepithelial cells. The myoepithelial cell is now recognised as being important in the regulation of growth, apoptosis and differentiation of luminal epithelial cells. Our hypothesis is that altered myoepithelial cell function could lead to reduced apoptosis and therefore a lower ability of the breast to remove cells with DNA damage, predisposing to cancer development.

To investigate the expression of myoepithelial proteins, immunohistochemistry was used to examine two series of NTCCB and equal numbers of age-matched normal breast controls, with a total of 180 tissues assessed. FGF2, IGF1, oestrogen receptor beta, p63, 14-3-3σ, glucocorticoid receptor and maspin were investigated. There was a significant difference in the expression of FGF2 (P = 0.02), with NTCCB having greater staining in both series of tissues. p63 was significantly different (P = 0.008) in one series but not the other. None of the other proteins showed a significant difference between the NTCCB and controls.

Myoepithelial cells are isolated from reduction mammoplasties and noninvolved tissue from mastectomies using positive selection [4]. Purity and changes in expression with passage have been checked by RT-PCR and immunocytochemistry for myoepithelial and luminal markers. Expression of FGF2 is being examined by quantitative PCR and western blotting. A limited study of the effects of conditioned media from myoepithelial cells from NTCCB and controls on breast cancer cell line growth and apoptosis has shown reduced induction of apoptosis by NTCCB, and these studies are being extended.

Myoepithelial cells from cancer-containing breast are different, particularly in expression of FGF2, which is being investigated further.