Cell lines:
- The pS2 gene is transcriptionally induced in MCF-7 cells by estrogen (Roberts M. et al., 1988).
- 3 stable ICI-182,780-resistant sub-lines were obtained from the
estrogen-receptor(ER)-positive and estrogen-responsive human breast-cancer MCF-7 BCC line submitted to long-term treatment with the pure steroidal anti-estrogen 10
-7 M ICI 182,780. All 3 resistant sub-lines had a lower basal expression of
cathepsin-D mRNA comparable with the lower
ER expression, but, in contrast, they have higher basal expression of the pS2 mRNA than the parent MCF-7 cell line. Although there are different basal expression levels of the pS2 and
cathepsin-D genes, the resistant sub-lines behave like the parent MCF-7 cell line with respect to the hormonal regulation of both genes (Larsen S.S. et al., 1997).
- In BCC, a local reorganization of the chromatin structure over pS2 and
cathepsin D promoters accompanies the establishment of the hormone-independent phenotype of the cells (Giamarchi C. et al., 1999).
- Genistein and quercetin are two well-known phyto-oestrogens. In MCF-7 BCC, genistein promoted transcription of the oestrogen-regulated genes pS2 and
cathepsin-D, whereas quercetin interfered with the oestrogen-induced expression of the proteins. More generally, it was concluded that quercetin acts like a pure anti-oestrogen, whereas genistein displays mixed agonist/antagonist properties in MCF-7 BCC (Miodini P. et al., 1999).
Tumors:
- TFF1 mRNA and protein expression are detected in approximately 50% of human breast tumors (Tomasetto C. et al., 1990).
- In a study of 59 ductal carcinoma in situ (DCIS) of the breast, positive staining for c-erbB-b2 and pS2 proteins was noted in 32% (19/59) and 46% (27/59) of DCIS, respectively. An inverse relationship between c-erbB-b2 and pS2 status in DCIS was observed. From the viewpoint of histological subtype, the prevalence of c-erbB-b2 protein expression was significantly higher in the comedo subtype than the cribriform-micropapillary subtype. The prevalence of immunoreactivity for c-erbB-b2 in solid subtype was intermediate between those of the other two groups. In contrast, the prevalence of pS2 expression was significantly lower in the comedo subtype than in the cribriform-micropapillary subtype. Again, the prevalence of pS2 protein expression in the solid subtype was intermediate between those of the other two subtypes (Inaji H. et al., 1996).
- Northern blotting was used to detect pS2 messenger ribonucleic acid (mRNA) in the primary tumour tissue from each of 90 patients with breast cancer. pS2 mRNA expression, present in 26 of 90 (29%) cancers, was associated with freedom from disease recurrence (P = 0.026) and was significantly associated with survival at a minimum of 6 years follow-up.
- pS2 (TFF1) protein and mRNA (determined by RT-PCR) levels were found to be significantly correlated in a series of 34 breast tumors. The mRNA levels for
ER,
PgR, and pS2 in breast tumors (n=100) were significantly correlated to each other, but none of them was associated with the mRNA expression of
PAI-1 (Tong D. et al., 1999).
Giamarchi C. et al. (1999) Chromatin structure of the regulatory regions of pS2 and
cathepsin D genes in hormone-dependent and -independent breast cancer cell lines. Oncogene 18, 533-541.
Inaji H. et al. (1996) Differential distribution of ErbB-2 and pS2 proteins in ductal carcinoma in situ of the breast. Breast Cancer Res. Treat. 37, 89-92.
Jakowlew S.B. et al. (1984) Sequence of the pS2 mRNA induced by estrogen in the human breast cancer cell line MCF-7. Nucleic Acids Res. 12, 2861-2878.
Jeltsch J.M. et al. (1987) Structure of the human oestrogen-responsive gene pS2. Nucleic Acids Res. 15, 1401-1414.
Larsen S.S. et al. (1997) Resistance of human breast-cancer cells to the pure steroidal anti-estrogen ICI 182,780 is not associated with a general loss of estrogen-receptor expression or lack of estrogen responsiveness. Int. J. Cancer 72, 1129-1136.
Lefebvre O. et al. (1996) Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein. Science 274, 259-262.
May F.E.B. and Westley B.R. (1997) Close physical linkage of the genes encoding the pNR-2/pS2 protein and human spasmolytic protein (hSP). Hum. Genet. 99, 303-307.
Miodini P. et al. (1999) The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function. Br. J. Cancer 80, 1150-1155.
Ribieras S. et al. (1998) The pS2/TFF1 trefoil factor, from basic research to clinical applications. Biochim. Biophys. Acta 1378, F61-F77 (
Review).
Roberts M. et al. (1988) The 5-prime flanking region of the human pS2 gene mediates its transcriptional activation by estrogen in MCF-7 cells. Biochem. Biophys. Res. Commun. 151, 306-313.
Seib T. et al. (1997) The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3. Genomics 40, 200-202.
Tomasetto C. et al. (1990) hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma. EMBO J. 9, 407-414.
Tong D. et al. (1999) Messenger RNA determination of
estrogen receptor,
progesterone receptor, pS2, and
plasminogen activator inhibitor-1 by competitive reverse transcription-polymerase chain reaction in human breast cancer. Clin. Cancer Res. 5, 1497-1502.
