Stimulatory effect of oestradiol-17β and tamoxifen on gross cystic disease fluid protein 15 000 production and mRNA levels in T47D human breast cancer cells

Abstract

Oestradiol-17 beta and tamoxifen regulate the synthesis of a gross cystic disease fluid protein (GCDFP-15) in T47D human breast cancer cells. Dose-response curves of GCDFP-15 mRNA contents and GCDFP-15 levels in culture media and cells versus hormone or antihormone concentration have been established. Production of GCDFP-15 was increased by oestradiol-17 beta, tamoxifen and 4-OH tamoxifen. The effect of tamoxifen and 4-OH tamoxifen was greater than the effect of oestradiol-17 beta. Moreover, oestradiol-17 beta and 4-OH tamoxifen acted synergystically in enhancing GCDFP-15 release. The strong oestrogenic effect of the antioestrogen tamoxifen in regulating GCDFP-15 may reflect an unusual interaction between the tamoxifen-oestrogen receptor complex and the DNA oestrogen-responsive elements. As oestrogen control of GCDFP-15 depends also on the cell line studied, investigation of GCDFP-15 could extend our knowledge of the possible mechanism of action of oestrogens or antioestrogens.

Prolactin-Induced Protein (PIP) Regulates Proliferation of Luminal A Type Breast Cancer Cells in an Estrogen-Independent Manner

“…The clinical significance of this observation is emphasized by reports that PIP expression is strongly enhanced upon tamoxifen treatment [34], [35], and that drug-resistant BCa cells continue to express PIP (Figure 5C). Targeting PIP may therefore prove effective not only in early disease stages, but also in advanced tumors resistant to hormonal therapy.…”

“…Furthermore, promotion of BCa cell proliferation by various hormones and growth factors may require the stimulation of PIP. Indeed, such stimulation has been observed in response to estrogens (Figure 5B; [34], [35]), androgens, prolactin and growth hormone [3], [4], [5], [9]. The identity and flexible nature of a common PIP function operative as an obligatory component of various growth stimulatory networks remains to be explored.…”

Mitogenic effect of the 15‐kDa gross cystic disease fluid protein (GCDFP‐15) on breast‐cancer cell lines and on immortal mammary cells

“…Interest in GCDFP-15 as been mainly focused on its secretion by breast cancer cells and the clinical evaluation of this protein as a tumor marker of a proportion of breast cancers, especially of those showing apocrine features (Haagensen et al, 1981(Haagensen et al, , 1990Mazoujian et al, 1983Mazoujian et al, , 1989Eusebi et al, 1986). Two breast-cancer cell lines secrete this protein (T47D and ZR75) and hormonal modulation of this secretion has been studied in both cell lines (Chablos et a/., Dejardin et al, 1991;Shiu et al, 1992;Haagensen et a/., 1992;Simard et al, 1989). To date, the only functional property identified for GCDFP-15 has been a binding affinity for fibrinogen (Haagensen et a/., 1981,1990).…”

“…The preneoplastic significance of gross cystic disease has been much discussed (Haagensen, 1991;Naldoni et al, 1992). The present study does not indicate a transformation potential for GCDFP-15.…”

“…Little is known regarding the function and biological significance of this apocrine marker. Evidence has been presented indicating that GCDFP-15 production is under hormonal control, since several hormones (androgens, estrogens and prolactin) can modulate its production in the T47D breastcancer cell line (Chablos et al, 1987;Dejardin et al, 1991;Shiu et al, 1992;Haagensen et aL, 1992). In addition, this protein has a remarkable affinity for fibrinogen (Haagensen et al, 1981;Haagensen et al, 1990).…”