Expression of human intestinal trefoil factor in malignant cells and its regulation by oestrogen in breast cancer cells

J Pathol. 1997 Aug;182(4):404-13. doi: 10.1002/(SICI)1096-9896(199708)182:4<404::AID-PATH875>3.0.CO;2-0.


Human intestinal trefoil factor (hITF) is a small cysteine-rich protein expressed in the gastrointestinal (GI) tract. Its sequence is related to that of other trefoil peptides including the pNR-2/pS2 protein, which is regulated by oestrogen in breast cancer. This study was designed to investigate whether hITF is expressed in human carcinoma cells. cDNA was obtained by reverse transcription-polymerase chain reaction (RT-PCR) of gastric mucosal RNA and sequenced, establishing that this mRNA 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 expressed in all the oestrogen-responsive but in none of the oestrogen-nonresponsive breast cancer cell lines. The possibility that hITF expression in breast cells is controlled by oestradiol was then tested. Oestradiol treatment increased hITF expression between three- and ten-fold 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 oestradiol but tamoxifen alone was a partial oestrogen agonist for hITF expression. These results show that hITF is expressed, sometimes ectopically, in several human malignancies, which suggests that trefoil peptides may have a more general role in tumourigenesis than hitherto appreciated. That the expression of hITF is regulated by oestrogen in breast cancer cells suggests that hITF expression may provide a novel marker for oestrogen responsiveness in breast cancer.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Breast Neoplasms / metabolism*
  • Carcinoma / metabolism*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Small Cell / metabolism
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology
  • Female
  • Gastric Mucosa / metabolism
  • Gene Expression / drug effects
  • Growth Substances / genetics*
  • Humans
  • Intestinal Neoplasms / metabolism*
  • Liver Neoplasms / metabolism
  • Lung Neoplasms / metabolism*
  • Molecular Sequence Data
  • Mucins*
  • Muscle Proteins*
  • Neuropeptides*
  • Peptides / genetics*
  • Polymerase Chain Reaction
  • Proteins / genetics
  • RNA, Messenger / analysis*
  • Stomach Neoplasms / metabolism*
  • Tamoxifen / pharmacology
  • Trefoil Factor-1
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins


  • Estrogen Antagonists
  • Growth Substances
  • Mucins
  • Muscle Proteins
  • Neuropeptides
  • Peptides
  • Proteins
  • RNA, Messenger
  • TFF1 protein, human
  • TFF3 protein, rat
  • Trefoil Factor-1
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Tumor Suppressor Proteins
  • Tamoxifen
  • Estradiol