EXPRESSION OF HUMAN INTESTINAL TREFOIL FACTOR IN MALIGNANT-CELLS AND ITS REGULATION BY ESTROGEN IN BREAST-CANCER CELLS

Human intestinal trefoil factor (hITF) is a small cysteine-rich protei n expressed in the gastrointestinal (GI) tract, Its sequence is relate d to that of other trefoil peptides including the pNR-2/pS2 protein, w hich is regulated by oestrogen in breast cancer. This study was design ed to investigate whether hITF is expressed in human carcinoma cells. cDNA,vas obtained by reverse transcription polymerase chain reaction ( RT-PCR) of gastric mucosal RNA and sequenced, establishing that this m RNA is expressed in the stomach, Expression of hITF was detected in a proportion of cell lines derived from malignancies of the GI tract, in hepatocellular carcinoma cells, and at highest levels in a small cell lung carcinoma cell Line, Amongst breast cancer cell lines, it was ex pressed in all the oestrogen-responsive but in none of the oestrogen-n onresponsive breast cancer cell lines, The possibility that hITF expre ssion in breast cells is controlled by oestradiol was then tested, Oes tradiol treatment increased hITF expression between three- and ten-fol d in the oestrogen-responsive breast cancer cell lines, demonstrating that, like pNR-2/pS2, hITF is regulated by oestrogen in breast cancer cells, Tamoxifen inhibited the induction of hITF expression by oestrad iol but tamoxifen alone was a partial oestrogen agonist for hITF expre ssion, These results show that hITF is expressed, sometimes ectopicall y, in several human malignancies, which suggests that trefoil peptides may have a more general role in tumourigenesis than hitherto apprecia ted, That the expression of hITF is regulated by oestrogen in breast c ancer cells suggests that hITF expression may provide a novel marker f or oestrogen responsiveness in breast cancer. (C) 1997 John Wiley & So ns, Ltd.