MITOGENIC EFFECT OF THE 15-KDA GROSS CYSTIC-DISEASE FLUID PROTEIN (GCDFP-15) ON BREAST-CANCER CELL-LINES AND ON IMMORTAL MAMMARY CELLS

The biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine met aplasia, i.e. the 15-kDa glycoprotein (GCDFP-15), is presently unknown . We have added GCDFP-15 to cell culture medium and tested its effect on proliferation of 4 human breast-cancer cell lines (MCF7, BT474, MDA -MB231 and T47D) and a ''normal'' human immortal breast-cell line (MCF 10A). These breast-cell lines showed a mitogenic response to GCDFP-15 (10 mu g/ml). GCDFP-15 enhanced cell growth of the MCF10A, MCF7, BT474 and MDA-MB231 cell lines at both 48 and 96 hr of exposure. The glycop rotein exerted a mitogenic effect on the T47D cell line at 48 hr but n ot at 96 hr. This may be due to an auto-regulatory effect of endogenou s GCDFP-15 synthesized by the T47D cells. GCDFP-15 was ineffective on 2 colon-cancer cell lines (HT29 and NIC-H716), on the IMR32 neuroblast oma cell line and on the NIC-H209 smatl-cell lung carcinoma cells. A s eparate major breast cystic disease fluid protein of 24 kDa (GCDFP-24) was tested, following the same experimental design, on the 5 breast-c ell lines, and showed no mitogenic activity. The mitogenic effect of G CDFP-15 observed in this study in both ''normal'' and malignant breast epithelial cells suggests a possible relationship between apocrine me taplasia in breast cystic disease and the development of breast epithe lial hyperplasia. In addition, a possible role of GCDFP-15 in breast-c ancer progression should be considered. (C) 1995 Wiley-Liss, Inc.