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

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Abstract
The biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine metaplasia, 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 (MCF10A). These breast‐cell lines showed a mitogenic response to GCDFP‐15 (10 μ/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 glycoprotein exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This may be due to an auto‐regulatory effect of endogenous GCDFP‐15 synthesized by the T47D cells. GCDFP‐15 was ineffective on 2 colon‐cancer cell lines (HT29 and NIC‐H7I6), on the IMR32 neuroblastoma cell line and on the NIC‐H209 small‐cell lung carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa (GCDFP‐24) was tested, following the same experimental design, on the 5 breast‐cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP‐15 observed in this study in both “normal” and malignant breast epithelial cells suggests a possible relationship between apocrine metaplasia in breast cystic disease and the development of breast epithelial hyperplasia. In addition, a possible role of GCDFP‐15 in breast‐cancer progression should be considered.