Association of pS2 (TFF1) release with breast tumour proliferative rate: in vitro and in vivo studies

Although cytosolic expression of the protein pS2 (TFF1) is considered to be a marker of oestrogen receptor (OR) function, there exists some clinical d ata to suggest an inverse relationship of cytosolic pS2 to tumour prolifera tion. Although secreted from breast cancer cells, the relationship of pS2 s ecretion to tumour natural history has been little studied. The mechanisms and kinetics of pS2 release and its relation to tumour cell proliferation w ere studied in a human breast cancer cell line MCF-7 and verified in a prel iminary clinical study. Stimulation by stripped serum or oestradiol resulte d in parallel increases of proliferation and pS2 release in both time cours e and dose-response experiments. Direct pharmacological alterations of prol iferation were followed by identical changes in pS2 release. The relationsh ip between serum pS2 levels and tumour proliferative activity when analysed as a function of steroid status showed a slope of 0.56 in OR+ vs. 0.19 in OR- tumours. It is concluded that pS2 release from breast cancer cells is a ssociated with their proliferation and measurement of serum pS2 levels migh t be a good predictor of tumour proliferative state and could permit noninv asive monitoring of this tumour parameter.